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.

Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morphometry from the ENIGMA consortium, we construct maps of cortical abnormalities for thirteen neurodevelopmental, neurological, and psychiatric disorders from N = 21,000 participants and N = 26,000 controls, collected using a harmonised processing protocol. We systematically compare cortical maps to multiple micro-architectural measures, including gene expression, neurotransmitter density, metabolism, and myelination (molecular vulnerability), as well as global connectomic measures including number of connections, centrality, and connection diversity (connectomic vulnerability). We find a relationship between molecular vulnerability and white-matter architecture that drives cortical disorder profiles. Local attributes, particularly neurotransmitter receptor profiles, constitute the best predictors of both disorder-specific cortical morphology and cross-disorder similarity. Finally, we find that cross-disorder abnormalities are consistently subtended by a small subset of network epicentres in bilateral sensory-motor, inferior temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local molecular attributes and global connectivity jointly shape cross-disorder cortical abnormalities.

Purpose The purpose of this study was to assess, in a large sample of healthy young adults, sex differences in the binding potential of [¹¹C]ABP688, a positron emission tomography (PET) tracer selective for the metabotropic glutamate type 5 (mGlu5) receptor. Methods High resolution [¹¹C]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 [¹¹C]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 [¹¹C]ABP688 is higher in healthy men than women. This likely represents a source of variability in [¹¹C]ABP688 studies and could have relevance for sex differences in cognitive-behavioral functions and neuropsychiatric disorders.

The positron emission tomography radioligand [¹¹C]UCB-J binds to synaptic vesicle glycoprotein 2 A (SV2A), a regulator of vesicle release. Increased neuronal firing could potentially affect tracer concentrations if binding site availability is altered during vesicle exocytosis. This study assessed whether physiological brain activation induces changes in [¹¹C]UCB-J tissue influx ( K₁), volume of distribution ( V_T), or binding potential ( BP_ND). Healthy volunteers ( n = 7) underwent 60-min [¹¹C]UCB-J PET scans at baseline and during intermittent presentation of 8-Hz checkerboard visual stimulation. Sensitivity to intermittent changes in kinetic parameters was assessed in simulations, and visual stimulation was repeated using functional magnetic resonance imaging to characterize neural responses. V_T and K₁ were determined using the one-tissue compartment model and BP_ND using the simplified reference tissue model. In primary visual cortex, K₁ increased 34.3 ± 15.5% ( p = 0.001) during stimulation, with no change in other regions ( ps > 0.12). K₁ change was correlated with fMRI BOLD response (r = 0.77, p = 0.043). There was no change in V_T (−3.9 ± 8.8%, p = 0.33) or BP_ND (−0.2 ± 9.6%, p = 0.94) in visual cortex nor other regions ( ps > 0.19). Therefore, despite robust increases in regional tracer influx due to blood flow increases, binding measures were unchanged during stimulation. [¹¹C]UCB-J V_T and BP_ND are likely to be stable in vivo measures of synaptic density.

Objective:Palivizumab is a prophylactic therapy shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations but has a high acquisition cost. The objective was to systematically examine the cost effectiveness of palivizumab in defined infant groups and identify important cost and outcome determinants.Methods:Literature searches of MedLine, the Cost-Effectiveness Analysis registry and the UK NHS Economic Evaluation Database (NHS EED) were conducted to identify economic evaluations of palivizumab compared to no prophylactic treatment for RSV prevention in any infant population. Study quality was evaluated using Quality of Health Economic Studies (QHES) criteria and results converted to 2009 CAN$ for comparison.Results:A total of 23 articles meeting inclusion criteria were identified, including 11 cost-utility analyses (CUAs) and 12 cost-effectiveness analyses (CEAs). Quality of individual analyses was fairly high (range 60–100, median 86). Results ranged from cost dominan...

From The Journal of Clinical Psychiatry: