Altered purinergic receptor expression in the frontal cortex in schizophrenia.

ATP functions as a neurotransmitter, acting on the ubiquitously expressed family of purinergic P2 receptors. In schizophrenia (SCZ), the pathways that modulate extracellular ATP and its catabolism to adenosine are dysregulated. However, the effects of altered ATP availability on P2 receptor expression in the brain in SCZ have not been assessed. We assayed P2 receptor mRNA and protein expression in the DLPFC and ACC in subjects diagnosed with SCZ and matched, non-psychiatrically ill controls (n = 20-22/group). P2RX7, P2RX4 and male P2RX5 mRNA expression were significantly increased (p < 0.05) in the DLPFC in SCZ. Expression of P2RX7 protein isoform was also significantly increased (p < 0.05) in the DLPFC in SCZ. Significant increases in P2RX4 and male P2RX5 mRNA expression may be associated with antipsychotic medication effects. We found that P2RX4 and P2RX7 mRNA are significantly correlated with the inflammatory marker SERPINA3, and may suggest an association between upregulated P2XR and neuroinflammation in SCZ. These findings lend support for brain-region dependent dysregulation of the purinergic system in SCZ.

Gene Enrichment Analysis of Astrocyte Subtypes in Psychiatric Disorders and Psychotropic Medication Datasets.

Astrocytes have many important functions in the brain, but their roles in psychiatric disorders and their responses to psychotropic medications are still being elucidated. Here, we used gene enrichment analysis to assess the relationships between different astrocyte subtypes, psychiatric diseases, and psychotropic medications (antipsychotics, antidepressants and mood stabilizers). We also carried out qPCR analyses and "look-up" studies to assess the chronic effects of these drugs on astrocyte marker gene expression. Our bioinformatic analysis identified gene enrichment of different astrocyte subtypes in psychiatric disorders. The highest level of enrichment was found in schizophrenia, supporting a role for astrocytes in this disorder. We also found differential enrichment of astrocyte subtypes associated with specific biological processes, highlighting the complex responses of astrocytes under pathological conditions. Enrichment of protein phosphorylation in astrocytes and disease was confirmed by biochemical analysis. Analysis of LINCS chemical perturbagen gene signatures also found that kinase inhibitors were highly discordant with astrocyte-SCZ associated gene signatures. However, we found that common gene enrichment of different psychotropic medications and astrocyte subtypes was limited. These results were confirmed by "look-up" studies and qPCR analysis, which also reported little effect of psychotropic medications on common astrocyte marker gene expression, suggesting that astrocytes are not a primary target of these medications. Conversely, antipsychotic medication does affect astrocyte gene marker expression in postmortem schizophrenia brain tissue, supporting specific astrocyte responses in different pathological conditions. Overall, this study provides a unique view of astrocyte subtypes and the effect of medications on astrocytes in disease, which will contribute to our understanding of their role in psychiatric disorders and offers insights into targeting astrocytes therapeutically.

A comparison of seminar and computer based training on the accuracy and reliability of raters using the Children's Global Assessment Scale (CGAS).

The aim of this study was to compare two methods to conduct CGAS rater training. A total of 648 raters were randomized to training (CD or seminar), and rated five cases before and 12 months after training. The ICC at baseline/end of study was 0.71/0.78 (seminar), 0.76/0.78 (CD), and 0.67/0.79 (comparison). There were no differences in training effect in terms of agreement with expert ratings, which speaks in favor of using the less resource-demanding CD. However, the effect was modest in both groups, and untrained comparison group improved of the same order of magnitude, which proposes more extensive training.

Children's Global Assessment Scale (CGAS) in a naturalistic clinical setting: Inter-rater reliability and comparison with expert ratings.

The Children's Global Assessment Scale (CGAS) is a tool to assess the overall level of functioning of children in Child and Adolescent Mental Health Services (CAMHS). Even though the use of this rating scale requires trained raters, it is commonly deployed without prior training in clinical settings. The aim of this study was to investigate the reliability and the agreement of CGAS ratings with an expert rating, in a clinical setting with untrained raters. Five experienced clinicians rated five vignettes to provide expert ratings. These vignettes were then rated by 703 health-care professionals representing 33 Swedish CAMHS. The health-care professionals rated the vignettes significantly higher (showing better global functioning) than the expert ratings. There was a wide range between the minimum and maximum ratings. The intraclass correlation coefficient was 0.73, which indicates moderate inter-rater reliability. Neither clinical experience nor earlier experience of using CGAS influenced the agreement with the expert ratings. The inter-rater reliability is moderate when CGAS is used in a clinical setting with untrained raters. Further, the untrained raters differed substantially from the experts. This stresses the importance of proper training in conjunction with the introduction of new rating scales.