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.

Black bile and psychomotor retardation: shades of melancholia in Dante's Inferno.

The history of melancholy depression is rich with images of movement retardation and mental dysfunction. The recent restoration of psychomotor symptoms to the diagnostic terminology of affective disorder is not novel to the students of medieval melancholia. The move back to the biology of this psychomotor dysfunction with the technical advances in brain imaging in recent years only echoes centuries-old writings on the centrality of movement changes in the depressive condition. The Inferno, the first cantica of Dante Alighieri's Commedia, has a wonderful abundance of allusions to the importance of psychomotor symptoms in describing the depressed individual. Slowed steps, garbled speech, frozen tears, these and many other images keep the physical manifestations of psychomotor suffering in the forefront of the reader's mind. Considering Medieval and Renaissance writings on melancholy suffering, it is fitting that Dante shows a bodily illness reflected in the hellish torments visited on the damned. From the souls of the sullen to those of the violent, the panorama of psychomotor symptoms plays a prominent role in the poem as well as in the medical and literary prose of succeeding centuries.