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Background: It is still unclear which underlying mechanisms are involved in cognitive deficits of psychotic disorders. Pro-cognitive effects of muscarinic M 1 receptor agonists suggest alterations in M 1 receptor functioning may modulate these symptoms. Post mortem studies in patients with schizophrenia have shown significantly reduced M 1 receptor expression rates in the dorsolateral prefrontal cortex (DLPFC) compared to controls. To date no in-vivo examinations of M 1 receptor binding in relation to cognitive impairments have been done. As cognitive deficits have similar course and prognostic relevance across psychotic disorders, the current study assessed M 1 receptor binding in the DLPFC and hippocampus in relation to cognitive functioning., Methods: Muscarinic M 1 receptor binding potential (BP ND ) was measured using 123 I-IDEX, single photon emission computed tomography (SPECT) in 30 medication-free subjects diagnosed with a psychotic disorder. A computerized neuropsychological test battery was used to assess cognition, and the positive and negative syndrome scale (PANSS) to assess severity of psychotic symptoms., Results: Assessment of cognitive domains showed that lower M 1 BP ND in the DLPFC was related to overall lower performance in verbal learning and memory. In addition, lower M 1 BP ND in the DLPFC was related to greater negative symptom severity. Lastly, lower M 1 BP ND in the hippocampus was related to worse delayed recognition of verbal memory., Conclusion: This is the first study to show that variation in M 1 receptors in the DLPFC is related to cognitive and negative symptom outcome in psychotic disorders. The M 1 receptor may be an important biomarker in biological stratification of patients with psychotic disorders.

Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20mg twice daily for 10 days) with (123)I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (P≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system., (Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.)

Background: Serotonin transporters (SERT) are a major target for antidepressant medication, although there have been limited in vivo studies of SERT availability in patients being treated with antidepressants. It is not known whether SERT availability differs in treatment-responsive and -nonresponsive patients receiving long-term treatment. In this study, we used single photon emission computed tomography (SPECT) to compare SERT residual availability in unipolar responders and nonresponders during long-term antidepressant treatment. Dopamine transporter (DAT) availability was also assessed in the same patients to examine the relationship between the two transporter systems., Methods: Twenty-four medicated unipolar patients were recruited, of whom 11 were responders and 13 were nonresponders. All patients underwent SPECT with [123I] beta-carbomethoxy-3-beta-(4 iodophenyl)tropane. Brain SERT was measured in the brain stem and diencephalon, and DAT was measured in the striatum. Residual availability was calculated as a ratio of specific to nonspecific uptake, with the occipital region used as the nonspecific reference region., Results: There was no difference between responders and nonresponders in SERT availability. Dopamine transporter availability was similar in responders and nonresponders, and there was no association between SERT and DAT availability., Conclusions: Serotonin transporter availability does not discriminate responders and nonresponders during long-term treatment with antidepressants.

Z-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridinyl)-2-propen-1-amine or zimelidine (ZIM) and its first metabolite nor-zimelidine, were radioiodinated via a nonisotopic exchange, using the Cu(I)-assisted nucleophilic labeling method. To evaluate their potential as SPECT ligands for the serotonin transporter (SERT), the biodistribution of both ligands was determined and pretreatment "blocking" studies performed. Both radioligands demonstrated a good brain penetration of 0.8-1% ID/g, stable after 60 min., p.i., and a brain/blood ratio of up to 3. In vivo brain distribution did not reveal specific binding. Blocking studies by pretreatment with a known SERT ligand, had minor influence on the uptake of [(123)I]I-ZIM, between the several isolated brain regions. It may therefore be concluded that [(123)I]I-ZIM and [(123)I]I-nor-ZIM do not appear to be promising SPECT ligands for the SERT.