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In this study, we aimed to test if the schizophrenia (SCZ) polygenic risk score (PRS) was associated with clinical symptoms in (a) the first episode of psychosis pre-treatment (FEP), (b) at nine weeks after initiation of risperidone treatment (FEP-9W) and (c) with the response to risperidone. We performed a detailed clinical assessment of 60 FEP patients who were antipsychotic-naive and, again, after nine weeks of standardized treatment with risperidone. After blood collection and DNA isolation, the samples were genotyped using the Illumina PsychArrayChip and then imputed. To calculate PRS, we used the latest available GWAS summary statistics from the Psychiatric Genomics Consortium wave-2 SCZ group as a training set. We used Poisson regression to test association between PRS and clinical measurements correcting for the four principal components (genotyping). We considered a p-value < 0.0014 (Bonferroni correction) as significant. First, we verified that the schizophrenia PRS was also able to distinguish cases from controls in this south-eastern Brazilian sample, with a similar variance explained to that seen in Northern European populations. In addition, within-cases analyses, we found that PRS is significantly correlated with baseline (pre-treatment) symptoms, as measured by lower clinical global assessment of functioning (−GAF), higher depressive symptoms and higher scores on a derived excitement factor. After standardized treatment for nine weeks, the correlation with GAF and the excitement factor disappeared while depressive symptoms became negatively associated with PRS. We conclude that drug (and other treatments) may confound attempts to understand the aetiological influence on symptomatology of polygenic risk scores. These results highlight the importance of studying schizophrenia, and other disorders, pre-treatment to understand the relationship between polygenic risk and phenotypic features.

The Carleton University Responsiveness to Suggestion Scale (CURSS) yields scores on three suggestibility dimensions. Objective (CURSS:0) scores and subjective (CURSS:S) scores reflect overt and experiential response to suggestion, respectively. Objective-Involuntariness (CURSS:OI) scores indicate the number of objective responses rated as feeling involuntary. Study 1 indicated that all three suggestibility dimensions correlated significantly with the Harvard Group Scale of Hypnotic Susceptibility, and Study 2 showed the three Catleton suggestibility dimensions correlated significantly with Form C of the Stanford Hypnotic Susceptibility Scale. The majority of subjects who obtained high scores on the Stanford:C also scored high on the Carleton suggestibility dimensions. Like the Harvard:A and Stanford:C the three Carleton suggestibility dimensions also correlated significantly with attitude/expectancy measures, absorption, and Field's (1965) “hypnotic experiences” inventory. CURSS:VC (voluntary-cooperation) scores reflect the number of objective responses rated as feeling primarily voluntary rather than involuntary. CURSS:VC scores did not correlate significantly with attitude/expectancy variables, absorption or “hypnotic experiences.” Theoretical implications are discussed.

Schizophrenia (SCZ) is a mental disorder arising from a complex interaction of genetic and environmental factors. It has been suggested that treatment-resistant schizophrenia (TRS) is a distinct, more severe, and homogenous subgroup of schizophrenia that could present specific biological markers. Our aim was to characterize expression of target genes in blood of TRS patients compared with non-TRS (NTRS) patients and healthy controls (HC). TRS has been defined using failure to respond to two previous antipsychotic trials. We hypothesized that genes involved in neurodevelopment, myelination, neuroplasticity, neurotransmission, and miRNA processing could be involved in treatment resistance; then, we investigated 13 genes related to those processes in 256 subjects, being 94 healthy controls and 162 schizophrenia patients treated with antipsychotics. Of those, 78 were TRS patients and 84 were NTRS patients. Peripheral blood samples were collected from all subjects and RNA was isolated. Gene expression analysis was performed using the TaqMan low-density array (TLDA) technology. To verify the influence of expression quantitative trait loci (eQTLs), we evaluated single-nucleotide polymorphism (SNP) of all genes using data from GTEx Project. SNP genotypes were obtained from HumanOmniExpress BeadChip. We did not detect gene expression differences between TRS and NTRS subjects, indicating candidate genes specific to treatment resistance. We detected an upregulation of CNR1 and UFD1L gene expression in patients (TRS and NTRS groups) when compared to controls, that may be associated with the release of neurotransmitters, which can influence neuronal plasticity, or with a stress response-activating protein degradation. DICER1 and AKT1 expression increased slightly across the groups and could differentiate only the extreme opposite groups, HC and TRS. Both genes act in heterogeneous pathways, such as cell signaling and miRNA processing, and seem to have an increased demand in the TRS group. We did not detect any eQTLs in our sample that could explain differences in mRNA levels, suggesting a possible regulation by other mechanism, not driven by genotypes. Our data strengthen the importance of several biological pathways involved in the schizophrenia refractoriness and severity, adding knowledge to develop more effective treatments in the future.

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Terminal microdeletions of the long arm of chromosome 6 are associated with a phenotype that includes multiple brain malformations, intellectual disability, and epilepsy. A 1.7-Mb region has been proposed to contain a gene responsible for the brain anomalies. Here, we present the case of a 12-year-old girl with multiple brain alterations and moderate intellectual disability with a 18-kb deletion in chromosome 6q27, which is smaller than the microdeletions previously described by microarray analysis. We refined the smallest region of overlap possibly associated with the phenotype of brain malformations and intellectual disability to a segment of 325 kb, comprising the <i>DLL1</i>,<i> PSMB1</i>,<i> TBP</i>, and<i> PDCD2 </i>genes since these genes were structurally and/or functionally lost in the smaller deletions described to date. We hypothesize that <i>DLL1</i> is responsible for brain malformations and possibly interacts with other adjacent genes. The <i>TBP</i> gene encodes a transcription factor which is potentially related to cognitive development. <i>TBP</i> is linked to <i>PSMB1 </i>and <i>PDCD2 </i>in a conserved manner among mammals, suggesting a potential interaction between these genes. In conclusion, the 6q27 microdeletion is a complex syndrome with variable expressivity of brain malformations and intellectual disability phenotypes which are possibly triggered by the 4 genes described and adjacent genes susceptible to gene regulation changes.