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The glutamate and γ‐aminobutyric acid neuroreceptor subtypes mGluR5 and GABAA are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non‐displaceable binding potential (BPND), and total distribution volume (VT) based on simultaneously acquired bolus‐infusion positron emission tomography (PET) and MR data. The pipeline was applied to [11C]ABP688‐PET/MR (13 healthy male non‐smokers, 26.6 ± 7.0 years) and [11C]Flumazenil‐PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as VT and BPND atlases of mGluR5 and GABAA, were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δABP = 3.0 ± 1.0% and δFMZ = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σABP = 4.0%–16.0%, σFMZ = 3.9%–9.5%). An evaluation of PET‐to‐PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [15O]H2O‐template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions. [ABSTRACT FROM AUTHOR]

Objective: A considerable body of research links cognitive function to dopaminergic transmission in the prefrontal cortex, but less is known about cognition in relation to striatal dopamine D2/3 receptors in unmedicated patients with psychosis.Methods: We investigated this association by obtaining PET recordings with the high-affinity D2/3 antagonist ligand [18F] fallypride in 15 medication-free patients with schizophrenia and 11 healthy controls. On the day of PET scanning, we undertook comprehensive neuropsychological testing and assessment of psychopathology using the Positive and Negative Syndrome Scale (PANSS).Results: The patients’ performance in cognitive tests was significantly impaired in almost all domains. Irrespective of medication history, the mean [18F] fallypride binding potential (BPND) in the patient group tended to be globally 5-10% higher than that of the control group, but without reaching significance in any brain region. There were significant positive correlations between individual patient performance in the Trail Making Test (TMT(A) and TMT(B)) and Digit-Symbol-Substitution-Test with regional [18F] fallypride BPND, which remained significant after Bonferroni correction for the TMT(A) in caudate nucleus (CN) and for the TMT(B) in CN and putamen. No such correlations were evident in the control group.Discussion: The association between better cognitive performance and greater BPND in schizophrenia patients may imply that relatively lower receptor occupancy by endogenous dopamine favors better sparing of cognitive function. Absence of comparable correlations in healthy controls could indicate a greater involvement of signaling at dopamine D2/3 receptors in certain cognitive functions in schizophrenia patients than in healthy controls. [ABSTRACT FROM AUTHOR]

Objectives: Off-label prescription of antipsychotics to patients without psychotic symptoms has become a routine matter for many psychiatrists and also some general practitioners. Nonetheless, little is known about the possibly detrimental effects of antidopaminergic medications on general psychopathology, subjective mental state, or a possible association with physiological parameters in nonpsychotic individuals. Methods: In this randomized, single-blinded study, groups of healthy volunteers (n=18) received low doses of reserpine, aripiprazole, haloperidol, or placebo on 7 successive days. Relevant physiological parameters (plasma prolactin, concentrations of catecholamine metabolites in plasma, and 24-hour urine) and each subject’s mental state (Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, visual analogue scale, Beck Depression Inventory II) were assessed at the start and end of the trial. Results: Of the three active treatments, only reserpine caused a significant increase in some plasma- and urine-catecholamine metabolites, but all three medications evoked objective and subjective changes in general psychopathology scores, which correlated with individual increases in plasma homovanillic acid concentrations. Both objective and subjective impairments were significantly more pronounced in the subgroup with greatest increase of plasma prolactin. Subjects experiencing the most pronounced side effects under haloperidol, which compelled them to drop out, showed significantly higher prolactin concentration increases than those who tolerated haloperidol well. Conclusion: We found consistent associations between altered markers of dopamine transmission and several objective and subjective mental impairments in healthy volunteers after 1 week’s treatment with antidopaminergic medications. These findings should draw attention to a more intensive risk–benefit evaluation in cases of off-label prescription of antipsychotic medications. [ABSTRACT FROM AUTHOR]

Cognitive impairments can be observed in the majority of diseases with disturbed dopamine transmission. They are considered as core symptoms of schizophrenia, a disorder in which they appear to be particularly pronounced. Their neurobiological background is not yet sufficiently investigated, but dopaminergic systems are believed to play a crucial role. The aim of this single-blind, randomised, placebo-controlled study was to examine the effects of subchronic antidopaminergic treatment on cognitive functions in healthy subjects. In total, 72 healthy volunteers, randomised into four groups, received one antidopaminergic substance (aripiprazole, haloperidol or reserpine) or placebo, respectively, for 7 days. A comprehensive neurocognitive assessment was conducted at baseline, 24 h after the last medication intake and 7 days later. In the Digit Symbol Substitution Test a distinct, statistically significant improvement was measured in the second session in the placebo but not in the medication group. A significant group*time interaction for reaction times in three subtests of the Test battery for Attentional Performance (TAP) was also found. Our findings indicate that modulation of dopaminergic systems affects primarily speed of information processing, attention and learning. Absence of effects on other functions, differing from previous reports, may be an expression of a sufficient counter-regulation. [ABSTRACT FROM AUTHOR]

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR 5 and GABA A are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non-displaceable binding potential (BP ND ), and total distribution volume (V T ) based on simultaneously acquired bolus-infusion positron emission tomography (PET) and MR data. The pipeline was applied to [ 11 C]ABP688-PET/MR (13 healthy male non-smokers, 26.6 ± 7.0 years) and [ 11 C]Flumazenil-PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as V T and BP ND atlases of mGluR 5 and GABA A , were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δ ABP  = 3.0 ± 1.0% and δ FMZ  = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σ ABP  = 4.0%-16.0%, σ FMZ  = 3.9%-9.5%). An evaluation of PET-to-PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [ 15 O]H 2 O-template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)