Linkage disequilibrium (LD) pattern of <i>AHI1</i> gene.

<p>Figures represent pairwise r² values observed in control subjects from German (a) and Spanish (b) origin. Values are represented in a grayscale ranging from white (no LD) to black (high LD).</p

Single alleles and haplotypes of the <i>AHI1</i> region associated with schizophrenia in the present study.

<p>Significant values are marked in bold. The corrected P-values are indicated in brackets.</p>a<p>To avoid redundant information, other significant haplotypes, which are variations of other larger significant haplotypes from this table, have not been included.</p>b<p>SNP27 had significantly different genotypic distributions in the German and the Spanish sample (heterogeneity <i>P</i> value = 0.016 uncorrected).</p><p>Abbreviations: Cont, control; SCZ, schizophrenia; ns, not significant; perm, permutation; ref, reference haplotype.</p

List of SNPs included in the present study.

<p>Abbreviations: CEU, CEPH collection - DNA samples of Utah residents with ancestry from northern and western Europe; MAF, minor allele frequency.</p

Genomic region and SNPs analyzed in this study.

<p>The position of each SNP is indicated with an orange arrow.</p

<i>AHI1</i> SNPs significantly associated with clinical traits in the Spanish sample.

<p>Significant <i>P</i> values (P<0.05) are indicated in bold.</p><p><b>^a</b>The corrected <i>P</i> value is indicated in brackets.</p><p>Abbreviations: SE, standard error; CI, confidence interval.</p

Serotonin (5-HT) neuron-specific inactivation of Cadherin-13 impacts 5-HT system formation and cognitive function

Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders