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Introduction: Urinary symptoms constitute the primary reason for female patients to consult their general practitioner. The urinary dipstick test serves as a cornerstone for diagnosing urinary tract infections (UTIs), yet traditional visual interpretation may be subject to variability. Automated devices for dipstick urinalysis are routinely used as alternatives, yet the evidence regarding their accuracy remains limited. Therefore we aimed to compare concordance between visual and automated urinary dipstick interpretation and determine their test characteristics for the prediction of bacteriuria., Material and Methods: We conducted a prospective validation study including urine samples originating from adult patients in general practice that were sent to the Maastricht Medical Centre + for urinary culture. Urinary dipstick tests were performed on each sample, which were interpreted visually and automatically. We calculated Cohen's κ and percentage agreement and used 2 × 2 tables to calculate test characteristics., Results: We included 302 urine samples. Visual and automated analysis showed almost perfect agreement (κ = 0.82 and κ = 0.86, respectively) for both nitrite and leukocyte esterase, but moderate agreement for erythrocytes (κ = 0.51). Interpretation of clinically relevant (nitrite and/or leukocyte esterase positive) samples showed almost perfect agreement (κ = 0.88). Urinary dipsticks show similar test characteristics with urinary culture as gold standard, with sensitivities of 0.92 and 0.91 and specificities of 0.37 and 0.41 for visual and automated interpretation respectively., Conclusion: Automated and visual dipstick analysis show near perfect agreement and perform similarly in predicting bacteriuria. However, automated analysis requires maintenance and occasionally measurement errors can occur.

Addictions are thought to be fostered by the emergence of poorly regulated mesocorticolimbic responses to drug-related cues. The development and persistence of these responses might be promoted by altered glutamate transmission, including changes to type 5 metabotropic glutamate receptors (mGluR5s). Unknown, however, is when these changes arise and whether the mGluR5 and mesocorticolimbic alterations are related. To investigate, non-dependent cocaine polydrug users and cocaine-naïve healthy controls underwent a positron emission tomography scan (15 cocaine users and 14 healthy controls) with [ 11 C]ABP688, and a functional magnetic resonance imaging scan (15/group) while watching videos depicting activities with and without cocaine use. For some drug videos, participants were instructed to use a cognitive strategy to lower craving. Both groups exhibited drug cue-induced mesocorticolimbic activations and these were larger in the cocaine polydrug users than healthy controls during the session's second half. During the cognitive regulation trials, the cocaine users' corticostriatal responses were reduced. [ 11 C]ABP688 binding was unaltered in cocaine users, relative to healthy controls, but post hoc analyses found reductions in those with 75 or more lifetime cocaine use sessions. Finally, among cocaine users (n = 12), individual differences in prefrontal [ 11 C]ABP688 binding were associated with midbrain and limbic region activations during the regulation trials. Together, these preliminary findings raise the possibility that (i) recreational polydrug cocaine users show biased brain processes towards cocaine-related cues and (ii) repeated cocaine use can lower cortical mGluR5 levels, diminishing the ability to regulate drug cue responses. These alterations might promote susceptibility to addiction and identify early intervention targets., (© 2023 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

The Personality Inventory for DSM-5-Brief Form (PID-5-BF) is a relatively novel measure assessing maladaptive personality traits. We examined whether PID-5-BF traits are associated with non-personality measures of wellbeing in N = 661 Canadian adults in the community. Depression, anxiety, and perceived stress measures were obtained, as were indices of alcohol and cannabis use. Symptoms of depression and perceived stress were associated with all PID-5-BF dimensions, except for antagonism. Anxiety symptoms were associated with negative affectivity (NA) and, to a lesser extent, psychoticism. A younger age and female sex were related to higher depression and stress scores. In contrast to the models assessing depressive, anxiety and stress symptoms, in which NA was the strongest contributor, no significant contribution of internalizing traits (i.e., PID-5-BF NA) on substance use outcomes was found when externalizing traits were included in the models. Specifically, binge drinking and cannabis use were associated with higher disinhibition scores and lower psychoticism scores. Regression models were substantially weaker for substance use than for the mood and stress symptoms. Younger individuals used more cannabis and males engaged in more binge drinking. These findings largely confirm PID-5-BF's construct validity, and indicate that various indices of wellbeing (not necessarily personality-associated measures) are associated with personality traits, as measured with the brief from of PID-5-BF., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The brain is composed of disparate neural populations that communicate and interact with one another. Although fiber bundles, similarities in molecular architecture, and synchronized neural activity all reflect how brain regions potentially interact with one another, a comprehensive study of how all these interregional relationships jointly reflect brain structure and function remains missing. Here, we systematically integrate 7 multimodal, multiscale types of interregional similarity ("connectivity modes") derived from gene expression, neurotransmitter receptor density, cellular morphology, glucose metabolism, haemodynamic activity, and electrophysiology in humans. We first show that for all connectivity modes, feature similarity decreases with distance and increases when regions are structurally connected. Next, we show that connectivity modes exhibit unique and diverse connection patterns, hub profiles, spatial gradients, and modular organization. Throughout, we observe a consistent primacy of molecular connectivity modes-namely correlated gene expression and receptor similarity-that map onto multiple phenomena, including the rich club and patterns of abnormal cortical thickness across 13 neurological, psychiatric, and neurodevelopmental disorders. Finally, to construct a single multimodal wiring map of the human cortex, we fuse all 7 connectivity modes and show that the fused network maps onto major organizational features of the cortex including structural connectivity, intrinsic functional networks, and cytoarchitectonic classes. Altogether, this work contributes to the integrative study of interregional relationships in the human cerebral cortex., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hansen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative atlas of 19 receptors and transporters across nine different neurotransmitter systems. We found that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting-state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncovered a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we found both expected and novel associations between receptor distributions and cortical abnormality patterns across 13 disorders. We replicated all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization., (© 2022. The Author(s).)

Objectives: Urinary tract infections (UTIs) are the most prevalent cause for women to consult a general practitioner (GP) and are commonly treated with (broad-spectrum) empirical antibiotics, even though 50% of UTIs are self-limiting. In this study, we aim to explore women's attitudes and experiences regarding UTIs, in order to determine patients' willingness to accept delayed antibiotic prescriptions., Design: An internet-based cross-sectional survey SETTING: We recruited participants during 2 weeks of March and April in 2020 through several social media platforms., Participants: We obtained 1476 responses, of which 975 were eligible for analysis., Results: We asked women about their knowledge, attitudes and practice regarding UTI-related symptoms. Participants ranked 'confirmation of diagnosis' (43.8%) as the most important reason to consult a GP with urinary symptoms, followed by 'pain relief' (32%), and 'antibiotic prescription' (14.3%). For treatment, 71% of participants reported that their GP prescribed immediate antibiotics, while only 3% received a delayed antibiotic prescription and 1% was advised pain medication. Furthermore, 50% of respondents were aware of the possible self-limiting course of UTIs and 70% would be willing to accept delayed antibiotic treatment, even if a certain diagnosis of UTI was established. Willingness to delay was lower in experienced patients compared to inexperienced patients., Conclusions: Women are quite receptive to delayed antibiotics as an alternative to immediate antibiotics for UTIs or urinary symptoms. GPs should consider discussing delayed antibiotic treatment more often with women presenting with urinary symptoms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Commonly comorbid early onset psychiatric disorders might reflect the varying expression of overlapping risk factors. The mediating processes remain poorly understood, but three factors show some promise: adolescent externalizing traits, early life adversity, and midbrain dopamine autoreceptors. To investigate whether these features acquire greater predictive power when combined, a longitudinal study was conducted in youth who have been followed since birth. Cohort members were invited to participate based on externalizing scores between 11 to 16 years of age. At age 18 (age 18.5 ± 0.6 y.o.), 52 entry criteria meeting volunteers had a 90-min positron emission tomography scan with [ 18 F]fallypride, completed the Childhood Trauma Questionnaire, and were assessed with the Structured Clinical Interview for DSM-5. The three-factor model identified those with a lifetime history of DSM-5 disorders with an overall accuracy of 90.4% (p = 2.4 × 10 -5 ) and explained 91.5% of the area under the receiver operating characteristic curve [95% CI: .824, 1.000]. Targeting externalizing disorders specifically did not yield a more powerful model than targeting all disorders (p = 0.54). The model remained significant when including data from participants who developed their first disorders during a three-year follow-up period (p = 3.5 × 10 -5 ). Together, these results raise the possibility that a combination of temperamental traits, childhood adversity, and poorly regulated dopamine transmission increases risk for diverse, commonly comorbid, early onset psychiatric problems, predicting this susceptibility prospectively., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Stimulant drug-paired cues can acquire the ability to activate mesocorticolimbic pathways and lead to new bouts of drug use. Studies in laboratory animals suggest that these effects are augmented by progressively greater drug use histories, impulsive personality traits, and acute drug ingestion. As a preliminary test of these hypotheses in humans, we exposed cocaine users (n = 14) and healthy volunteers (n = 10) to cocaine-related videos during two functional magnetic resonance imaging (fMRI) sessions, once following acute administration of placebo and once following d-amphetamine (0.3 mg/kg, p.o.). Across sessions, cocaine users showed larger cocaine cue-induced responses than healthy controls in the associative striatum and midbrain. Among the cocaine users, larger drug cue-induced responses during the placebo session were correlated with higher Barratt Impulsiveness Scale (BIS-11) nonplanning scores (associative striatum) and greater lifetime use of stimulant drugs (limbic, associative, and sensorimotor striatum). The administration of d-amphetamine did not augment the cue-induced activations, but, in cocaine users, drug cue-induced striatal activations were more widespread following prolonged cocaine cue exposure. Together, these effects of past and present drug use might aggravate the risk for stimulant drug use problems., (© 2021 Society for the Study of Addiction.)

Objective: Only a minority of drug and alcohol users develops a substance use disorder. Previous studies suggest that this differential vulnerability commonly reflects a developmental trajectory characterized by diverse externalizing behaviors. In this study, we examined the relation between child and adolescent externalizing behaviors and adolescent substance use in a prospectively followed Canadian birth cohort, accounting for the temporal sequence of a wide variety of contributing factors., Methods: Two hundred and forty-two adolescents followed since birth (date range: 1996 to 2012) were assessed on externalizing behavior (age 17 months to 16 years), alcohol and cannabis use at age 16, age of alcohol use onset, family history of substance use problems, family functioning (age 11 to 15), sensation seeking (age 16), prenatal substance exposure, socioeconomic status (age 1 to 9), and sex., Results: Age of alcohol use onset was predicted by a family history of substance use problems, externalizing traits from ages 6 to 10 and 11 to 16, sensation seeking at age 16, prenatal alcohol and tobacco exposure and family functioning at ages 11 to 15. High frequencies of alcohol and cannabis use at age 16 were both predicted by externalizing traits from ages 11 to 16, a family history of substance use problems and sensation seeking after controlling for other individual, environmental and familial variables. The association between familial substance use problems and substance use during adolescence was partially mediated by externalizing traits from age 11 to 16., Conclusions: The present findings provide prospective evidence for a developmental risk pathway for adolescent substance use, potentially identifying those who could benefit from early interventions.

Objective: Besides hyperlipidemia, inflammation is an important determinant in the initiation and the progression of atherosclerosis. As Neuroimmune Guidance Cues (NGCs) are emerging as regulators of atherosclerosis, we set out to investigate the expression and function of inflammation-regulated NGCs. Methods and results: NGC expression in human monocytes and endothelial cells was assessed using a publicly available RNA dataset. Next, the mRNA levels of expressed NGCs were analyzed in primary human monocytes and endothelial cells after stimulation with IL1β or TNFα. Upon stimulation a total of 14 and 19 NGCs in monocytes and endothelial cells, respectively, were differentially expressed. Since plexin A4 (PLXNA4) was strongly downregulated in endothelial cells under inflammatory conditions, the role of PLXNA4 in endothelial function was investigated. Knockdown of PLXNA4 in endothelial cells markedly impaired the integrity of the monolayer leading to more elongated cells with an inflammatory phenotype. In addition, these cells showed an increase in actin stress fibers and decreased cell-cell junctions. Functional assays revealed decreased barrier function and capillary network formation of the endothelial cells, while vascular leakage and trans-endothelial migration of monocytes was increased. Conclusion: The current study demonstrates that pro-inflammatory conditions result in differential expression of NGCs in endothelial cells and monocytes, both culprit cell types in atherosclerosis. Specifically, endothelial PLXNA4 is reduced upon inflammation, while PLXNA4 maintains endothelial barrier function thereby preventing vascular leakage of fluids as well as cells. Taken together, PLXNA4 may well have a causal role in atherogenesis that deserves further investigation., Competing Interests: GH has served as consultant and speaker for biotech and pharmaceutical companies that develop molecules that influence lipoprotein metabolism, including Regeneron, Pfizer, MSD, Sanofi, and Amgen. Until April 2019, GH has served as PI for clinical trials conducted with A.O. Amgen, Sanofi, Eli Lilly, Novartis, Kowa, Genzyme, Cerenis, Pfizer, Dezima, Astra Zeneca. The Department of Vascular Medicine receives the honoraria and investigator fees for sponsor studies/lectures for companies with approved lipid lowering therapy in the Netherlands. Since April 2019, GH is partly employed by Novo Nordisk and the AMC. GH has no active patents nor share or ownership of listed companies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vreeken, Bruikman, Stam, Cox, Nagy, Zhang, Postma, van Zonneveld, Hovingh and van Gils.)

This study sought to examine if mental health issues, namely depression and anxiety symptoms, and loneliness were experienced differently according to various demographic groups during the COVID-19 pandemic (i.e., a societal stressor). An online survey, comprising demographic questions and questionnaires on depression, anxiety and loneliness symptoms, was distributed in Canada during the height of social distancing restrictions during the COVID-19 pandemic. Respondents (N=661) from lower income households experienced greater anxiety, depression and loneliness. Specifically, loneliness was greater in those with an annual income <$50,000/yr versus higher income brackets. Younger females (18-29yr) displayed greater anxiety, depressive symptoms and loneliness than their male counterparts; this difference did not exist among the other age groups (30-64yr, >65yr). Moreover, loneliness scores increased with increasing depression and anxiety symptom severity category. The relationship between loneliness and depression symptoms was moderated by gender, such that females experienced higher depressive symptoms when encountering greater loneliness. These data identify younger females, individuals with lower income, and those living alone as experiencing greater loneliness and mental health challenges during the height of the pandemic in Canada. We highlight the strong relationship between loneliness, depression and anxiety, and emphasize increased vulnerability among certain cohorts., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The excitatory neurotransmitter glutamate has been implicated in experience-dependent neuroplasticity and drug-seeking behaviors. Type 5 metabotropic glutamate (mGlu5) receptors might be particularly important. They are critically involved in synaptic plasticity and their availability has been reported to be lower in people with alcohol, tobacco, and cocaine use disorders. Since these reductions could reflect effects of drug use or pre-existing traits, we used positron emission tomography to measure mGlu5 receptor availability in young adults at elevated risk for addictions. Fifty-nine participants (age 18.5 ± 0.6) were recruited from a longitudinal study that has followed them since birth. Based on externalizing traits that predict future substance use problems, half were at low risk, half were at high risk. Cannabis use histories varied markedly and participants were divided into three subgroups: zero, low, and high use. Compared to low risk volunteers, those at elevated risk had lower [ 11 C]ABP688 binding potential (BP ND ) values in the striatum, amygdala, insula, and orbitofrontal cortex (OFC). Cannabis use by risk group interactions were observed in the striatum and OFC. In these regions, low [ 11 C]ABP688 BP ND values were only seen in the high risk group that used high quantities of cannabis. When these high risk, high cannabis use individuals were compared to all other participants, [ 11 C]ABP688 BP ND values were lower in the striatum, OFC, and insula. Together, these results provide evidence that mGlu5 receptor availability is low in youth at elevated risk for addictions, particularly those who frequently use cannabis.

The molecular basis of atherosclerosis is not fully understood and mice studies have shown that Ephrins and EPH receptors play a role in the atherosclerotic process. We set out to assess the role for monocytic EPHB2 and its Ephrin ligands in human atherosclerosis and show a role for EPHB2 in monocyte functions independently of its EphrinB ligands. Immunohistochemical staining of human aortic sections at different stages of atherosclerosis showed that EPHB2 and its ligand EphrinB are expressed in atherosclerotic plaques and that expression proportionally increases with plaque severity. Functionally, stimulation with EPHB2 did not affect endothelial barrier function, nor did stimulation with EphrinB1 or EphrinB2 affect monocyte-endothelial interactions. In contrast, reduced expression of EPHB2 in monocytes resulted in decreased monocyte adhesion to endothelial cells and a decrease in monocyte transmigration, mediated by an altered morphology and a decreased ability to phosphorylate FAK. Our results suggest that EPHB2 expression in monocytes results in monocyte accumulation by virtue of an increase of transendothelial migration, which can subsequently contribute to atherosclerotic plaque progression., (© 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology.)

The neurobiological traits that confer risk for addictions remain poorly understood. However, dopaminergic function throughout the prefrontal cortex, limbic system, and upper brainstem has been implicated in behavioral features that influence addiction vulnerability, including poor impulse control, and altered sensitivity to rewards and punishments (i.e., externalizing features). To test these associations in humans, we measured type-2/3 dopamine receptor (DA 2/3 R) availability in youth at high vs. low risk for substance use disorders (SUDs). In this study, N = 58 youth (18.5 ± 0.6 years) were recruited from cohorts that have been followed since birth. Participants with either high (high EXT; N = 27; 16 F/11 M) or low pre-existing externalizing traits (low EXT; N = 31; 20 F/11 M) underwent a 90-min positron emission tomography [ 18 F]fallypride scan, and completed the Barratt Impulsiveness Scale (BIS-11), Substance Use Risk Profile scale (SURPS), and Sensitivity to Punishment (SP) and Sensitivity to Reward (SR) questionnaire. We found that high vs. low EXT trait participants reported elevated substance use, BIS-11, SR, and SURPS impulsivity scores, had a greater prevalence of psychiatric disorders, and exhibited higher [ 18 F]fallypride binding potential (BP ND ) values in prefrontal, limbic and paralimbic regions, even when controlling for substance use. Group differences were not evident in midbrain dopamine cell body regions, but, across all participants, low midbrain BP ND values were associated with low SP scores. Together, the results suggest that altered DA 2/3 R availability in terminal extra-striatal and dopamine cell body regions might constitute biological vulnerability traits, generating an EXT trajectory for addictions with and without co-occurring alterations in punishment sensitivity (i.e., an internalizing feature).

Purpose: To determine how the low-affinity (Z)-isomer of the radiotracer [ 11 C]ABP688 affects binding potential values in vivo in humans., Methods: High-resolution [ 11 C]ABP688 PET scans were acquired on 74 healthy volunteers (25 male, 49 female, mean age 20 ± 3.0). The relative contents of (E)- and (Z)-isomers were determined prior to injection using analytical high-performance liquid chromatography [r t (E) = 10 min, r t (Z) = 8.5 min]. Mean binding potential [BP ND  = f ND * (B avail /K D )] values were calculated in the striatum, limbic regions, and prefrontal cortex using the simplified reference tissue model with cerebellar grey matter as reference., Results: Mean ± SD (E)-isomer content in [ 11 C]ABP688 production was 92 ± 3.8% (range 78-97%). Percent (E)-isomer was positively correlated with BP ND in the striatum (ρ = 0.28, p = 0.015) and limbic regions (ρ = 0.25, p = 0.036). In multiple regression analysis, sex (β = 0.39, p = 0.001) and (E)-isomer content (β = 0.23, p = 0.040) were significant predictors of BP ND ., Conclusions: Even modest levels of (Z)-[ 11 C]ABP688 can reduce estimates of tracer binding in vivo. Future studies should use production methods that enrich levels of (E)-[ 11 C]ABP688, report tracer isomer ratios, and account for this factor in their analyses.

Purpose: The purpose of this study was to assess, in a large sample of healthy young adults, sex differences in the binding potential of [ 11 C]ABP688, a positron emission tomography (PET) tracer selective for the metabotropic glutamate type 5 (mGlu5) receptor., Methods: High resolution [ 11 C]ABP688 PET scans were acquired in 74 healthy volunteers (25 male, 49 female, mean age 20 ± 3.0). Mean binding potential (BP ND  = f ND * (B avail / K D )) values were calculated in the prefrontal cortex, striatum, and limbic regions using the simplified reference tissue model with cerebellar grey matter as the reference region., Results: [ 11 C]ABP688 BP ND was significantly higher in men compared to women in the prefrontal cortex (p < 0.01), striatum (p < 0.001), and hippocampus (p < 0.05). Whole-brain BP ND was 17% higher in men. BP ND was not related to menstrual phase in women., Conclusions: Binding availability of mGlu5 receptors as measured by PET [ 11 C]ABP688 is higher in healthy men than women. This likely represents a source of variability in [ 11 C]ABP688 studies and could have relevance for sex differences in cognitive-behavioral functions and neuropsychiatric disorders.

Objective: Recently identified mutations of the axon guidance molecule receptor gene, DCC, present an opportunity to investigate, in living human brain, mechanisms affecting neural connectivity and the basis of mirror movements, involuntary contralateral responses that mirror voluntary unilateral actions. We hypothesized that haploinsufficient DCC +/- mutation carriers with mirror movements would exhibit decreased DCC mRNA expression, a functional ipsilateral corticospinal tract, greater "mirroring" motor representations, and reduced interhemispheric inhibition. DCC +/- mutation carriers without mirror movements might exhibit some of these features., Methods: The participants (n = 52) included 13 DCC +/- mutation carriers with mirror movements, 7 DCC +/- mutation carriers without mirror movements, 13 relatives without the mutation or mirror movements, and 19 unrelated healthy volunteers. The multimodal approach comprised quantitative real time polymerase chain reaction, transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) under resting and task conditions, and measures of white matter integrity., Results: Mirror movements were associated with reduced DCC mRNA expression, increased ipsilateral TMS-induced motor evoked potentials, increased fMRI responses in the mirroring M1 and cerebellum, and markedly reduced interhemispheric inhibition. The DCC +/- mutation, irrespective of mirror movements, was associated with reduced functional connectivity and white matter integrity., Interpretation: Diverse connectivity abnormalities were identified in mutation carriers with and without mirror movements, but corticospinal effects and decreased peripheral DCC mRNA appeared driven by the mirror movement phenotype. ANN NEUROL 2019;85:433-442., (© 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

[ 11 C]ABP688 is a positron emission tomography (PET) radioligand that binds selectively to metabotropic glutamate type 5 receptors (mGluR5). The use of this tracer has identified receptor binding changes in clinical populations, and has been informative in drug occupancy studies. However, previous studies have found significant increases in [ 11 C]ABP688 binding in the later scan of same-day comparisons, and estimates of test-retest reliability under consistent scanning conditions are not available. The objective of this study was to assess the variability of [ 11 C]ABP688 binding in healthy people in scans performed at the same time of day. Two [ 11 C]ABP688 scans were acquired in eight healthy volunteers (6 women, 2 men) using a high-resolution research tomograph (HRRT). Scans were acquired 3 weeks apart with start times between 10:00am and 1:30pm. Mean mGluR5 binding potential (BP ND ) values were calculated across cortical, striatal and limbic brain regions. Participants reported on subjective mood state after each scan and blood samples were drawn for cortisol analysis. No significant change in BP ND between scans was observed. Variability in BP ND values of 11-21% was observed across regions, with the greatest change in the hippocampus and amygdala. Reliability was low to moderate. BP ND was not statistically related to scan start time, subjective anxiety, serum cortisol levels, or menstrual phase in women. Overall, [ 11 C]ABP688 BP ND estimates show moderate variability in healthy people. Reliability is fair in cortical and striatal regions, and lower in limbic regions. Future research using this ligand should account for this in study design and analysis., (© 2018 Wiley Periodicals, Inc.)

It has been proposed that the acquisition of drug seeking is related to the development of conditioned dopamine responses in the ventral striatum. As drug use continues and becomes habit-like, conditioned responses have been shown to shift to the dorsal striatum. Here, using the PET [ 11 C]raclopride method and highly personalized cocaine cues, we report the first evidence in humans of the dorsal dopamine response prior to the onset of addiction.