Abstract
BackgroundNegative symptoms (NS) are central for the symptomatology of schizophrenia associated with poor functional outcome. Two dimensions of NS have consistently been proposed: apathy and diminished expression. Even though distinct pathophysiological mechanism have been hypothesised resting state perfusion and dimensions of NS have not been studied. Here, we therefore focused on dimensions of NS and the link to whole brain resting state perfusion in schizophrenia patients.MethodsWe included 45 schizophrenia spectrum patients and 44 age- and gender-matched healthy controls. We assessed NS with the Scale for the Assessment of Negative Symptoms (SANS) and imaging on a 3T MRI scanner. Apathy was currently present in 31 patients and diminished expression in 27 patients. Patients did not differ in antipsychotic medication or positive symptoms. We compared whole-brain perfusion over all, and between the groups using 1-way ANCOVAs (F and T tests). A uniform threshold of p < 0.5 (FWE-corr) was applied.ResultsDiminished expression was most prominently associated with perfusion within the right orbital cortex, insula, ventral striatum and head of caudate nucleus, while apathy was associated with perfusion bilateral within the SMA, the insula and the thalamus.DiscussionDimensions of NS at rest were associated with altered resting state perfusion, in particular in brain areas relevant for reward processing. Distinguishable associations of rCBF with NS dimensions point to distinct underlying pathophysiology.
Highlights
Cognitive deficits contribute to aversive social behaviors such as impulsive aggression
Participants (N=28) with schizophrenia or schizoaffective disorder were recruited from New York Presbyterian Hospital and Manhattan Psychiatric Center and randomized into one of two cognitive training groups—a cognitive remediation training plus social cognition training (CRT+SCT) group versus CRT alone
We indexed emotion regulation capacity using the Positive and Negative Affect Scale (PANAS) and by obtaining heart rate, respiration, and electrodermal activity while participants viewed pictures selected from the International Affective Picture System (IAPS)
Summary
D1 receptors, which couple to inhibitory G-proteins, have been shown to regulate neuronal growth and development, mediate some behavioral responses. We report the evaluation in non-human primates of [18F]MNI-968 (PF-06730110), a novel PET radiotracer of the D1 receptors Methods: Four brain PET studies, 2 baselines and 2 blockade studies using PF-2562, a D1 partial agonist compound, were conducted for 90 min in two rhesus monkeys with [18F]MNI-968 (169 ± 31 MBq). For the blockade studies in rhesus monkeys, occupancy was estimated from BPND at baseline and post blockade. All three quantification methods (2T, LGA and NI-LGA) were in excellent agreement, with a similar estimated D1 receptors occupancy of PF-06730110 of ~40% for both monkeys in the caudate and putamen. In human, [18F]MNI-968 kinetics appeared to be faster compared to nonhuman primates, with a BPND in the putamen of ~0.8. Discussion: Our work showed that [18F]MNI-968 ([18F]PF-06730110), is a promising agonist PET radiotracer for imaging D1agnist receptors that can be quantified non-invasively. Vanessa Cropley*,1, Eleni Ganella, Cassandra Wannan, Andrew Zalesky, Tamsyn Van Rheenen, Chad Bousman, Ian Everall, Alexander Fornito, Christos Pantelis5 1The University of Melbourne; 2University of Calgary; 3Institute of Psychiatry, Psychology & Neuroscience, King’s College London; 4School of Psychology and Psychiatry & Monash Biomedical Imaging, Monash University; 5Melbourne Neuropsychiatry Centre, University of Melbourne
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