Anxiety as a neurodevelopmental disorder in a neuronal subpopulation: Evidence from gene expression data.

The relationship between genes and anxious behavior, is nor linear nor monotonic. To address this problem, we analyzed with a meta-analytic method the literature data of the behavior of knockout mice, retrieving 33 genes whose deletion was accompanied by increased anxious behavior, 34 genes related to decreased anxious behavior and 48 genes not involved in anxiety. We correlated the anxious behavior resulting from the deletion of these genes to their brain expression, using the Allen Brain Atlas and Gene Expression Omnibus (GEO) database. The main finding is that the genes accompanied, after deletion, by a modification of the anxious behavior, have lower expression in the cerebral cortex, the amygdala and the ventral striatum. The lower expression level was putatively due to their selective presence in a neuronal subpopulation. This difference was replicated also using a database of human gene expression, further showing that the differential expression pertained, in humans, a temporal window of young postnatal age (4 months up to 4 years) but was not evident at fetal or adult human stages. Finally, using gene enrichment analysis we also show that presynaptic genes are involved in the emergence of anxiety and postsynaptic genes in the reduction of anxiety after gene deletion.