Lithium response in lymphoblastoid cell line samples.

<p>ANCOVA analysis was performed to compare the three groups (Controls, Responders, and Non-responders to lithium treatment) separately for Syn2a and Syn2b expression. The variables “Age at sampling” and “LCL frozen storage” were used as covariates.</p

Cell lines expression for SYN2b.

<p>Expression in (A) HEK293 embryonic kidney cells, (B) SK-N-AS neuroblastoma cells, and (C) and U-118 MG glioblastoma/astrocytoma cells for the Synapsin IIb variant compared to GAPDH. P-values depicting the mean differences between 3 independent experiments for each cell line at each of the 3 treatment concentration of either lithium or vehicle (0.5 mM, 1.0 mM, and 2.0 mM).</p

Cell lines expression for SYN2a.

<p>Expression in (A) HEK293 embryonic kidney cells, (B) SK-N-AS neuroblastoma cells, and (C) and U-118 MG glioblastoma/astrocytoma cells for the Synapsin IIa variant compared to GAPDH. P-values depicting the mean differences between 3 independent experiments for each cell line at each of the 3 treatment concentration of either lithium or vehicle (0.5 mM, 1.0 mM, and 2.0 mM).</p

Additional file 2: Table S2. of DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression

Mixed Model ANOVA results for SYN1, SYN2, and SYN3 promoter CpG methylation. A. SYN1: Type III Tests of Fixed Effects. B. SYN2: Type III Tests of Fixed Effects. C. SYN3: Type III Tests of Fixed Effects. (XLSX 11 kb

Additional file 1: Table S1. of DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression

Diagnostic group statistics and comparisons. No difference between potential confounders. Normality of each variable was computed per each diagnostic group. When the data were normally distributed, unpaired Student’s T-tests were performed, and when at least one group was not normally distributed (Shapiro-Wilk p-value ≤0.05), non-parametric tests were performed. Differences in Gender were tested with Fisher’s Exact tests. (XLSX 12 kb

Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity

Basal progenitors (BPs), including intermediate progenitors and basal radial glia, are generated from apical radial glia and are enriched in gyrencephalic species like humans, contributing to neuronal expansion. Shortly after generation, BPs delaminate towards the subventricular zone, where they further proliferate before differentiation. Gene expression alterations involved in BP delamination and function in humans are poorly understood. Here, we study the role of LGALS3BP, so far known as a cancer biomarker, which is a secreted protein enriched in human neural progenitors (NPCs). We show that individuals with LGALS3BP de novo variants exhibit altered local gyrification, sulcal depth, surface area and thickness in their cortex. Additionally, using cerebral organoids, human fetal tissues and mice, we show that LGALS3BP regulates the position of NPCs. Single-cell RNA-sequencing and proteomics reveal that LGALS3BP-mediated mechanisms involve the extracellular matrix in NPCs' anchoring and migration within the human brain. We propose that its temporal expression influences NPCs' delamination, corticogenesis and gyrification extrinsically. </p

Results of the INRICH pathway analysis.

<p>Results of the INRICH pathway analysis are shown in bar plot format. The x-axis shows negative logarithmic enrichment p-values for all nominally associated pathways containing two and more genes prior to- (gray) and after- (blue) correction for multiple testing. The red horizontal line indicates a p-value of 0.05.</p

Results of the Ingenuity Pathway Analysis.

<p>Results of the Ingenuity Pathway Analysis (IPA) are shown in bar plot format. The x-axis shows negative logarithmic enrichment p-values for all associated pathways containing two and more genes prior to- (gray) and after- (blue) Benjamini Hochberg correction for multiple testing. The red horizontal line indicates a p-value of 0.05.</p

IPA pathway synaptic long term potentiation.

<p>Results of the Ingenuity pathway analysis (IPA) for the pathway “Synaptic Long Term Potentiation” are shown. Shared schizophrenia-bipolar disorder associated genes (<i>GRIN2A</i>, <i>GRM3</i>, <i>CACNA1C</i>) are highlighted in purple.</p