Description of a control experiment, designed to test the effect of size on the expression of the ERP components presented in this document.

<p>Description of a control experiment, designed to test the effect of size on the expression of the ERP components presented in this document.</p

ERPs elicited by novel and standard stimuli after administration of apomorphine and placebo, at electrodes Fz and Cz.

<p>Time is indexed on the x-axis in milliseconds; zero indicates stimulus onset. ERP magnitude is indexed on the y-axis in microvolts (µV). For all the ERP plots, the continuous line corresponds to the Apomorphine condition and the dotted line to placebo. A. ERPs to novel stimuli at Fz electrode. Additionally the topography of the difference between apomorphine and placebo conditions is presented, as calculated from 140 ms to 220 ms. B. ERPs to standard stimuli at Fz electrode. C. ERPs to novel stimuli at Cz electrode. Additionally the topography of the difference between apomorphine and placebo conditions is presented, as calculated from 350 ms to 450 ms. D. ERPs to standard stimuli at Cz electrode.</p

Schematic representation of the testing session and task (cutout).

<p>Words were presented once every 3.5 seconds. Some words, shown here in white, had a unique font and color (novel font). During the presentation of each word, a sound was played with a variable delay after word presentation. For most words this was a standard sound, for some a unique sound (novel sound, shown here with Volcano).</p

Behavioral data. Accuracy (%) is presented in the y-axis, and bars are plotted for novel and standard stimuli, both under apomorphine and placebo.

<p>Error bars represent the standard error of the mean of the individual means.</p

Metabolites concentrations (mean/SD) in the DLPFC and hippocampal region in healthy controls and 22q11DS with and without psychosis.

<p>HC: Healthy controls SCZ−: 22q11DS without psychosis SCZ+: 22q11DS with psychosis.</p><p>Glu: glutamate Gln: glutamine Glx: Glu+Gln NAA: <i>N</i>-acetylaspartate.</p><p>NAA+NAAG: NAA+<i>N</i>-acetylaspartylglutamate mI: myo-inositol Cr: creatine Cho: choline.</p><p>Metabolite concentrations are expressed in millimoles per liter.</p>a<p><i>P</i><0.05 for SCZ− <i>vs.</i> SCZ+.</p>b<p><i>P</i> = 0.05 for HC <i>vs.</i> SCZ+.</p

Sample of a 1H-MRS spectrum from hippocampus of a patient with 22q11DS as fit by LCModel.

<p>Sample of a 1H-MRS spectrum from hippocampus of a patient with 22q11DS as fit by LCModel.</p

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies