Kraepelinian theory posits that schizophrenia (SZ) is a degenerative disorder that worsens throughout the lifespan. Behavioral studies of cognition have since challenged that viewpoint, particularly in the early phases of illness. Nonetheless, the extent to which cognition remains functionally stable during the early course of illness is unclear, particularly with regard to task-associated connectivity in cognition-related brain networks. In this study, we examined the 1-year stability of the frontoparietal control network during the AX-Continuous Performance Task (AX-CPT) from a new baseline sample of 153 participants scanned at 3T, of which 29 recent onset individuals with SZ and 42 healthy control (HC) participants had follow-up data available for analysis. Among individuals that had both baseline and follow-up data, reduced functional connectivity in SZ was observed between the dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex (SPC) during the high control (B cue) condition. Furthermore, this deficit was stable over time, as no significant time × diagnosis interaction or effects of time were observed and intraclass correlation coefficients were greater than 0.6 in HCs and SZ. Previous 1.5T findings showing stable deficits with no evidence of degeneration in performance or DLPFC activation in an independent SZ sample were replicated. Overall, these results suggest that the neuronal circuitry supporting cognitive control is stably impaired during the early course of illness in SZ across multiple levels of analysis with no evidence of functional decline.

A primary goal of psychiatry is to better understand the pathways that link genetic risk to psychiatric symptoms. Here, we tested association of diagnosis and endophenotypes with overall and neurotransmitter pathway-specific polygenic risk in patients with early-stage psychosis. Subjects included 205 demographically diverse cases with a psychotic disorder who underwent comprehensive psychiatric and neurological phenotyping and 115 matched controls. Following genotyping, we calculated polygenic scores (PGSs) for schizophrenia (SZ) and bipolar disorder (BP) using Psychiatric Genomics Consortium GWAS summary statistics. To test if overall genetic risk can be partitioned into affected neurotransmitter pathways, we calculated pathway PGSs (pPGSs) for SZ risk affecting each of four major neurotransmitter systems: glutamate, GABA, dopamine, and serotonin. Psychosis subjects had elevated SZ PGS versus controls; cases with SZ or BP diagnoses had stronger SZ or BP risk, respectively. There was no significant association within psychosis cases between individual symptom measures and overall PGS. However, neurotransmitter-specific pPGSs were moderately associated with specific endophenotypes; notably, glutamate was associated with SZ diagnosis and with deficits in cognitive control during task-based fMRI, while dopamine was associated with global functioning. Finally, unbiased endophenotype-driven clustering identified three diagnostically mixed case groups that separated on primary deficits of positive symptoms, negative symptoms, global functioning, and cognitive control. All clusters showed strong genome-wide risk. Cluster 2, characterized by deficits in cognitive control and negative symptoms, additionally showed specific risk concentrated in glutamatergic and GABAergic pathways. Due to the intensive characterization of our subjects, the present study was limited to a relatively small cohort. As such, results should be followed up with additional research at the population and mechanism level. Our study suggests pathway-based PGS analysis may be a powerful path forward to study genetic mechanisms driving psychiatric endophenotypes.

Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text]. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 [Formula: see text], and sleptons up to 260 [Formula: see text], depending on the model details.