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Background Altered cerebral blood flow (CBF) has been found in people at risk for psychosis, with first-episode psychosis (FEP) and with chronic schizophrenia (SCZ). Studies using arterial spin labelling (ASL) have shown reduction of cortical CBF and increased subcortical CBF in SCZ. Previous studies have investigated CBF using ASL in FEP, reporting increased CBF in striatum and reduced CBF in frontal cortex. However, as these people were taking antipsychotics, it is unclear whether these changes are related to the disorder or antipsychotic treatment and how they relate to treatment response. Methods We examined CBF in FEP free from antipsychotic medication (N = 21), compared to healthy controls (N = 22). Both absolute and relative-to-global CBF were assessed. We also investigated the association between baseline CBF and treatment response in a partially nested follow-up study (N = 14). Results There was significantly lower absolute CBF in frontal cortex (Cohen's d = 0.84, p = 0.009) and no differences in striatum or hippocampus. Whole brain voxel-wise analysis revealed widespread cortical reductions in absolute CBF in large cortical clusters that encompassed occipital, parietal and frontal cortices (Threshold-Free Cluster Enhancement (TFCE)-corrected r = 0.67, p = 0.008). Conclusions These results show lower cortical absolute perfusion in FEP prior to starting antipsychotic treatment and suggest relative-to-global frontal CBF as assessed with magnetic resonance imaging could potentially serve as a biomarker for antipsychotic response.

Evidence from post-mortem studies and in vivo imaging studies suggests there may be reducedIn this study, we investigated the relationship between hippocampal NMDAR and striatal glutamate using simultaneous positron emission tomography-magnetic resonance (PET-MR) imaging. We recruited 40 volunteers to this cross-sectional study; 21 patients with schizophrenia, all in their first episode of illness, and 19 healthy controls. We measured hippocampal NMDAR availability using the PET ligand [A total of 33 individuals (15 healthy controls, 18 patients) were included in the analyses (mean (SD) age of controls, 27.31 (4.68) years; mean (SD) age of patients, 24.75 (4.33), 27 male and 6 female). We found an inverse relationship between hippocampal DVR and striatal glutamate levels in people with first-episode psychosis (rho = -0.74,This study show that lower relative NMDAR availability in the hippocampus may drive increased striatal glutamate levels in patients with schizophrenia. Further work is required to determine whether these findings may yield new targets for drug development in schizophrenia.

Background: Evidence from post-mortem studies and in vivo imaging studies suggests there may be reduced N-methyl-d-aspartate receptor (NMDAR) levels in the hippocampus in patients with schizophrenia. Other studies have reported increased glutamate in striatum in schizophrenia patients. It has been hypothesised that NMDAR hypofunction leads to the disinhibition of glutamatergic signalling; however, this has not been tested in vivo. Methods: In this study, we investigated the relationship between hippocampal NMDAR and striatal glutamate using simultaneous positron emission tomography-magnetic resonance (PET-MR) imaging. We recruited 40 volunteers to this cross-sectional study; 21 patients with schizophrenia, all in their first episode of illness, and 19 healthy controls. We measured hippocampal NMDAR availability using the PET ligand [18F]GE179. This was indexed relative to whole brain as the distribution volume ratio (DVR). Striatal glutamatergic indices (glutamate and Glx) were acquired simultaneously, using combined PET-MR proton magnetic resonance spectroscopy (1H-MRS). Results: A total of 33 individuals (15 healthy controls, 18 patients) were included in the analyses (mean (SD) age of controls, 27.31 (4.68) years; mean (SD) age of patients, 24.75 (4.33), 27 male and 6 female). We found an inverse relationship between hippocampal DVR and striatal glutamate levels in people with first-episode psychosis (rho = −0.74, p Conclusion: This study show that lower relative NMDAR availability in the hippocampus may drive increased striatal glutamate levels in patients with schizophrenia. Further work is required to determine whether these findings may yield new targets for drug development in schizophrenia.

Posterior reversible encephalopathy syndrome (PRES) is a variable etiology clinical syndrome with similar neuroimaging results and clinical symptoms. PRES can develop in both adults and children and is characterized by headaches, disorders of consciousness, seizures and especially focal visual disturbances, often associated with hypertensive state. In most cases, symptoms resolve without neurological consequences. The treatment strategy concerns early diagnosis and general measures to correct the underlying cause of PRES. Here, we report a case of PRES that occurs in a 6-year-old child with nephrotic syndrome.

[18F]FDOPA PET imaging has shown dopaminergic function indexed asKicerdiffers between antipsychotic treatment responders and non-responders. However, the theragnostic potential of this biomarker to identify non-responders has yet to be evaluated. In view of this, we aimed to evaluate this as a theragnostic test using linear and non-linear machine-learning (i.e., Bernoulli, support vector, random forest and Gaussian processes) analyses and to develop and evaluate a simplified approach, standardised uptake value ratio (SUVRc). Both [18F]FDOPA PET approaches had good test-rest reproducibility across striatal regions (KicerICC: 0.68–0.94, SUVRc ICC: 0.76–0.91). Both our linear and non-linear classification models showed good predictive power to distinguish responders from non-responders (receiver operating curve area under the curve for region-of-interest approach:Kicer = 0.80, SUVRc = 0.79; for voxel-wise approach using a linear support vector machine: 0.88) and similar sensitivity for identifying treatment non-responders with 100% specificity (Kicer: ~50%, SUVRc: 40–60%). Although the findings were replicated in two independent datasets, given the total sample size (n = 84) and single setting, they warrant testing in other samples and settings. Preliminary economic analysis of [18F]FDOPA PET to fast-track treatment-resistant patients with schizophrenia to clozapine indicated a potential healthcare cost saving of ~£3400 (equivalent to $4232 USD) per patient. These findings indicate [18F]FDOPA PET dopamine imaging has potential as biomarker to guide treatment choice.

Although antipsychotic drugs are effective for relieving the psychotic symptoms of first-episode psychosis (FEP), psychotic relapse is common during the course of the illness. While some FEPs remain remitted even without medication, antipsychotic discontinuation is regarded as the most common risk factor for the relapse. Considering the actions of antipsychotic drugs on presynaptic and postsynaptic dopamine dysregulation, this study evaluated possible mechanisms underlying relapse after antipsychotic discontinuation. Twenty five FEPs who were clinically stable and 14 matched healthy controls were enrolled. Striatal dopamine activity was assessed as Kicer value using [18F]DOPA PET before and 6 weeks after antipsychotic discontinuation. The D2/3 receptor availability was measured as BPND using [11C]raclopride PET after antipsychotic discontinuation. Healthy controls also underwent PET scans according to the corresponding schedule of the patients. Patients were monitored for psychotic relapse during 12 weeks after antipsychotic discontinuation. 40% of the patients showed psychotic relapse after antipsychotic discontinuation. The change in Kicer value over time significantly differed between relapsed, non-relapsed patients and healthy controls (Week*Group: F = 4.827, df = 2,253.193, p = 0.009). In relapsed patients, a significant correlation was found between baseline striatal Kicer values and time to relapse after antipsychotic discontinuation (R2 = 0.518, p = 0.018). BPND were not significantly different between relapsed, non-relapsed patients and healthy controls (F = 1.402, df = 2,32.000, p = 0.261). These results suggest that dysfunctional dopamine autoregulation might precipitate psychotic relapse after antipsychotic discontinuation in FEP. This finding could be used for developing a strategy for the prevention of psychotic relapse related to antipsychotic discontinuation.

N-methyl-D-aspartate receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. To address this, we studied 40 volunteers (21 patients with first-episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE-179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Hippocampal DVR, but not VT, was significantly lower in patients relative to controls (p = 0.02, Cohen’s d = 0.81; p = 0.15, Cohen’s d = 0.49), and negatively associated with total (rho = −0.47, p = 0.04), depressive (rho = −0.67, p = 0.002), and general symptom severity (rho = −0.74, p

Preclinical models of psychosis propose that hippocampal glutamatergic neuron hyperactivity drives increased striatal dopaminergic activity, which underlies the development of psychotic symptoms. The aim of this study was to examine the relationship between hippocampal glutamate and subcortical dopaminergic function in people at clinical high risk for psychosis, and to assess the association with the development of psychotic symptoms. 1H-MRS was used to measure hippocampal glutamate concentrations, and 18F-DOPA PET was used to measure dopamine synthesis capacity in 70 subjects (51 people at clinical high risk for psychosis and 19 healthy controls). Clinical assessments were undertaken at baseline and follow-up (median 15 months). Striatal dopamine synthesis capacity predicted the worsening of psychotic symptoms at follow-up (r = 0.35; p p = 0.13). There were no differences in either glutamate (p = 0.5) or dopamine (p = 0.5) measures in the total patient group relative to controls. Striatal dopamine synthesis capacity at presentation predicts the subsequent worsening of sub-clinical total and psychotic symptoms, consistent with a role for dopamine in the development of psychotic symptoms, but is not strongly linked to hippocampal glutamate concentrations.

There have been few studies performed to examine the pathophysiological differences between different types of psychosis, such as between delusional disorder (DD) and schizophrenia (SZ). Notably, despite the different clinical characteristics of DD and schizophrenia (SZ), antipsychotics are deemed equally effective pharmaceutical treatments for both conditions. In this context, dopamine dysregulation may be transdiagnostic of the pathophysiology of psychotic disorders such as DD and SZ. In this study, an examination is made of the dopamine synthesis capacity (DSC) of patients with SZ, DD, other psychotic disorders, and the DSC of healthy subjects. Fifty-four subjects were recruited to the study, comprising 35 subjects with first-episode psychosis (11 DD, 12 SZ, 12 other psychotic disorders) and 19 healthy controls. All received an 18F-DOPA positron emission tomography (PET)/magnetic resonance (MR) scan to measure DSC (Kocc;30–60 value) within 1 month of starting antipsychotic treatment. Clinical assessments were also made, which included Positive and Negative Syndrome Scale (PANSS) measurements. The mean Kocc;30–60 was significantly greater in the caudate region of subjects in the DD group (ES = 0.83, corrected p = 0.048), the SZ group (ES = 1.40, corrected p = 0.003) and the other psychotic disorder group (ES = 1.34, corrected p = 0.0045), compared to that of the control group. These data indicate that DD, SZ, and other psychotic disorders have similar dysregulated mechanisms of dopamine synthesis, which supports the utility of abnormal dopamine synthesis in transdiagnoses of these psychotic conditions.

Although antipsychotic drugs are effective for relieving the psychotic symptoms of first-episode psychosis (FEP), psychotic relapse is common during the course of the illness. While some FEPs remain remitted even without medication, antipsychotic discontinuation is regarded as the most common risk factor for the relapse. Considering the actions of antipsychotic drugs on presynaptic and postsynaptic dopamine dysregulation, this study evaluated possible mechanisms underlying relapse after antipsychotic discontinuation. Twenty five FEPs who were clinically stable and 14 matched healthy controls were enrolled. Striatal dopamine activity was assessed as K

Introduction. With biomedical imaging research increasingly using large datasets, it becomes critical to find operator-free methods to quality control the data collected and the associated analysis. Attempts to use artificial intelligence (AI) to perform automated quality control (QC) for both single-site and multi-site datasets have been explored in some neuroimaging techniques (e.g. EEG or MRI), although these methods struggle to find replication in other domains. The aim of this study is to test the feasibility of an automated QC pipeline for brain [18F]-FDOPA PET imaging as a biomarker for the dopamine system. Methods. Two different Convolutional Neural Networks (CNNs) were used and combined to assess spatial misalignment to a standard template and the signal-to-noise ratio (SNR) relative to 200 static [18F]-FDOPA PET images that had been manually quality controlled from three different PET/CT scanners. The scans were combined with an additional 400 scans, in which misalignment (200 scans) and low SNR (200 scans) were simulated. A cross-validation was performed, where 80% of the data were used for training and 20% for validation. Two additional datasets of [18F]-FDOPA PET images (50 and 100 scans respectively with at least 80% of good quality images) were used for out-of-sample validation. Results. The CNN performance was excellent in the training dataset (accuracy for motion: 0.86 ± 0.01, accuracy for SNR: 0.69 ± 0.01), leading to 100% accurate QC classification when applied to the two out-of-sample datasets. Data dimensionality reduction affected the generalizability of the CNNs, especially when the classifiers were applied to the out-of-sample data from 3D to 1D datasets. Conclusions. This feasibility study shows that it is possible to perform automatic QC of [18F]-FDOPA PET imaging with CNNs. The approach has the potential to be extended to other PET tracers in both brain and non-brain applications, but it is dependent on the availability of large datasets necessary for the algorithm training.

AimsEvidence from genetics, post mortem and animal studies suggest that N-Methyl-D-Aspartate Receptor (NMDAR) hypofunction has an important role in the pathophysiology of psychosis. However, it is not known if NMDAR activity is altered in the early stages of psychosis or if this links to symptom severity. Our aim was to investigate NMDAR availability in first-episode psychosis (FEP) and determine if it links to symptom severity. The NMDAR hypofunction hypothesis of schizophrenia was initially proposed in the 1990s on the basis of observations that ketamine and phencyclidine (PCP) induced the full range of schizophrenia-like symptoms (positive, negative and cognitive) when given to healthy participants and also that they worsen symptoms in patients with schizophrenia.MethodWe recruited 40 volunteers, including 21 patients with schizophrenia from early intervention services in London (12 antipsychotic-free and 9 receiving antipsychotic medication) and 19 matched healthy controls. The uptake of an NMDAR selective ligand, [18F]GE179, was measured using positron emission tomography (PET) and indexed using the distribution volume ratio (DVR) and volume of distribution (VT, in millilitres per cubic centimetre) of [18F]GE179 in the hippocampus and additional exploratory regions (anterior cingulate cortex (ACC), thalamus, striatum and temporal lobe). Symptom severity was measured using the Positive and Negative Syndrome Scale (PANSS).ResultA total of 37 individuals were included in the analyses (mean [SD] age of controls, 26.7 [4.5] years; mean [SD] age of patients, 25.3 [4.9] years). There was a significant reduction in hippocampal DVR in the patients with schizophrenia relative to healthy controls (p = 0.02, Cohen's d = 0.81). Although the VT of [18F]GE179 was lower in absolute terms in patients, there was no significant effect of group on VT in the hippocampus (p = 0.15, Cohen's d = 0.49) or the exploratory brain regions. There was a negative association between hippocampal DVR and total PANSS symptoms (rho = –0.47, p = 0.04), depressive symptoms (rho = –0.67, p = 0.002), and general PANSS symptoms (rho = –0.74, p = 0.001).ConclusionThese results indicate lower hippocampal NMDAR levels in schizophrenia relative to controls with a large effect size, and that lower NMDAR levels are associated with greater levels of symptom severity. These findings are consistent with the role of NMDAR hypofunction in the pathophysiology of schizophrenia; however, further work is required to test specificity and causal relationships.

In the context of experimental PET imaging, continuously arterial blood sampling is often performed to obtain a time-continuous description of the radiotracer blood activity following its administration. This information is important to quantify the delivery of the tracer into tissues through the kinetic modelling analysis. With the introduction of simultaneous PET-MRI scanners, a new generation of automatic blood samplers compatible with the high magnetic field of the equipment has been introduced; however, the signal-to-noise ratio (SNR) of these counters is much poorer. In this work we extend an existing pipeline of blood modelling (called “MultiBlood”) to the analysis of arterial blood data obtained from MR-compatible samplers. We show that this method can filter out the excess of noise and return blood data time-activity courses comparable with the previous generation of blood samplers.

Background Abnormal Cerebral Blood Flow (CBF) has been found in patients with chronic schizophrenia (SCZ), first-episode psychosis patients (FEP) and individuals at clinical high-risk (CHR). In particular, previous studies using Arterial Spin Labelling (ASL) found that SCZ have a global reduction of CBF in the cortex and increased CBF in the basal ganglia, the hippocampus, and the amygdala as compared with controls. To date, only one study investigated CBF using ASL in a small cohort of medicated FEP reporting increased CBF in the striatum and reduced frontal CBF as compared with controls. However, it is still not clear whether these abnormalities are related to antipsychotic treatment or rather they reflect a disease state independent from medication. Critically, clinical and pre-clinical evidence suggests that antipsychotics increase CBF, especially in the basal ganglia through dopamine D2 receptors blockade. Here, we assessed CBF differences between FEP and controls in a larger cohort of unmedicated or minimally treated patients. In addition, we tested the association between CBF abnormalities and clinical features. Methods 26 FEP (13 medication-free, 9 antipsychotics naïve, 4 minimally treated) and 22 healthy controls (HC) were recruited. FEP and HC were matched for age and gender. Among FEP, 11 had a diagnosis of affective psychosis and 15 of non-affective psychosis. MRI scans were acquired using a GE MR750 3T scanner and a 12-channel head coil. ASL data was acquired using a pseudo-continuous ASL sequence (pCASL). Four control-label pairs were used. Quantification of the CBF data was made using a coil sensitivity map and a proton density image. CBF maps were normalized using non-linear registration and smoothed using a 6 mm full width at half maximum (FWHM) kernel. Grey matter CBF and regional CBF values in each Region of Interest (ROI) were extracted using individual grey matter images and WFU-Pickatlas ROIs with the MarsBar toolbox. Based on previous studies the following ROIs were selected: right and left hippocampus, right and left striatum, right and left frontal cortex. Whole-brain voxel-wise analysis was performed using a non-parametric independent t-test as implemented in FSL randomize (Threshold Free Cluster Enhancement, TFCE, and 5000 permutations). Bonferroni method was used to correct ROI analysis for multiple comparisons (alpha = 0.05, n = 7). Results Significantly reduced CBF was found in FEP as compared with controls in total grey matter CBF (p = 0.004). Whole-brain voxel-wise analysis FEP-HC comparison revealed a widespread cortical reduction in large cortical clusters that encompass the occipital, parietal and frontal cortices (pFWE TFCE corrected < 0.05). ROI analysis revealed a significant reduction in CBF in the right frontal cortex (p = 0.002). A nominal significant reduction was also detected in the left frontal cortex (p = 0.014). No statistically significant differences were found in the other ROI considered (all p > 0.1). Sub-analysis after removing minimally treated patients did not change the results. Both global grey matter CBF and right frontal CBF were reduced in both affective and non-affective psychosis as compared with controls (p < 0.05), whereas no differences were detected between the two clinical groups. Discussion Our results confirm earlier evidence on reduction of cortical perfusion in FEP. However, in contrast with previous studies, we did not detect any difference in striatal perfusion in our cohort of unmedicated/minimally treated patients. Hence, our results support the hypothesis that alteration in striatal perfusion are likely due to medication. Finally, our results suggest that CBF alterations might have a trans-diagnostic role in the pathophysiology of psychosis.

Aim No data are available on caffeine consumption among Italian adolescents. We investigated caffeine intake from coffee, soft drinks and energy drinks in a sample of Italian adolescents and determined if they exceeded the recommended limits. Methods The study comprised 1213 adolescents with a mean age of 15.1 years (range 12–19) from four schools in Foggia, southern Italy. Caffeine intake was assessed using an anonymous self-reported questionnaire during the 2013/2014 school year. We calculated the percentage of daily caffeine consumers, their mean intake of caffeine from beverages and the contribution of each beverage category to the total caffeine intake. Results Approximately 76% of the sample consumed caffeine every day, amounting to 125.5 ± 69.2 mg/day and 2.1 ± 1.2 mg/kg/day. When we applied the reference values from the Academy of Pediatrics, we found that 46% of the adolescents exceeded the recommended upper limits. Coffee was the most frequently consumed caffeinated drink and the main contributor to daily caffeine intake. Conclusion More than three quarters (76%) of the Italian adolescents in our study drank coffee on a daily basis and nearly half (46%) exceeded the recommended upper limits. Strategies are needed to reduce caffeine consumption by adolescents.

Introduction the prevalence of malnutrition in children and its impact on clinical outcomes is underrecognized by clinicians in Italy as well as worldwide. A novel definition of pediatric malnutrition has been recently proposed by a working group of the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), based on the correlation between illness and the use of zscores of anthropometric measurements. Aim to investigate the prevalence of malnutrition and related nutritional support among hospitalized children in Italy, in a nationwide survey performed in a single day (16/4/2015). Methods an open access website (http://nday.biomedia.net) was used to collected data from 73 hospitals and 101 wards in 14 Italian regions (1994 patients). Anonymous information was collected on hospitals' characteristics, patient's anthropometry, admission diagnosis, presence of chronic diseases and use of nutritional support: oral nutritional supplements (ONS), enteral nutrition (EN) or parenteral nutrition (PN). Z-scores of anthropometric measurements, calculated with Epi Info 7.1.5, defined nutritional status: wasting was identified by BMI or Weight-for-Length z-score (

Angelo Campanozzi1,∗, Irene Rutigliano1, Clementina Calabrese1, Maria Pia Falcone1, Barbara Santangelo1, Nicola D’Altilia1, Paolo Tonti2, Antonio Pennella3, Mario D’Altilia4, Michele Carmine Sacco4, Massimo Pettoello-Mantovani1 1 Clinica Pediatrica, Universita’ di Foggia, Foggia, Italy 2 U.O. Gastroenterologia, Ospedali Riuniti di Foggia, Foggia, Italy 3 Anatomia Patologica, Universita’ di Foggia, Foggia, Italy 4 Pediatria, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

PP30 – Table 1 Glucose Insulin HOMA Cholesterol Triglyceride TNF-α 6-keto PG (mg/dl) (μUI/ml) (mg/dl) (mg/dl) (pg/ml) (pg/ml) Group A (76 pts) 89.3±6.6 14.6±7.7 3.2±1.7 161±29 105.4±60 10.1±5.4 185.1±24.1 (44 pts) Group B (80 pts) 88.0±8.5 11.0±5.8 2.4±1.3 162±32 85.4±50 14±7.5 492.6±91.8 (26 pts) p NS 0.001 0.002 NS 0.025 NS 0.002 and cirrhosis) usually occur in middle and late age, atherosclerotic process in the vascular wall and liver damage might begin very early in obese children. Aim of the study: was to investigate, in children attending our outpatient clinic for obesity, 1) any early vascular structural change and the presence of fatty liver; 2) any possible metabolic risk factor. Patients and methods: the study population consisted of 156 children (71 girls), whose BMI z-score was 4.5±1.4 and their mean age was 8.2±2.7 years. They all underwent ultrasonography to measure the intima-media thickness (IMT) of carotids and to study the morphology of the liver. Their serum glucose, insulin, HOMA index, lipids, TNF-α were measured as well. For those who gave their consent (70 pts), 6-keto PGF 1α was also evaluated. Results: according to IMT measurement, patients were divided in Group A (0.6-0.7 mm) with a BMI z-score of 4.6±1.4* and Group B (0.4-0.5 mm) with a BMI z-score of 4.1±0.9* (*p= 0.2). Their data are reported in Table 1. Liver steatosis was present in 23/76 pts of Group A (30.2%) and in 11/80 pts of Group B (13.7%) Conclusions: Increased carotid IMT was documented in 76/156 children (48.7%) and fatty liver in 34/156 (21.8%). Fasting insulin levels, HOMA index, triglyceride levels and 6-Keto-PGF1α were significantly different between Group A and Group B. These data might suggest that higher insulin resistance and triglyceride levels, together with low levels of 6-keto PGF 1α could be considered risk factors for early vascular damage and hepatic steatosis in obese children.