Depression, a devastating psychiatric disorder, is a leading cause of disability worldwide. Current antidepressants address specific symptoms of the disease, but there is vast room for improvement . In this respect, new compounds that act beyond classical antidepressants to target signal transduction pathways governing synaptic plasticity and cellular resilience are highly warranted. The extracellular signal-regulated kinase (ERK) pathway is implicated in mood regulation, but its pleiotropic functions and lack of target specificity prohibit optimal drug development. Here, we identified the transcription factor ELK-1, an ERK downstream partner , as a specific signaling module in the pathophysiology and treatment of depression that can be targeted independently of ERK. ELK1 mRNA was upregulated in postmortem hippocampal tissues from depressed suicides; in blood samples from depressed individuals, failure to reduce ELK1 expression was associated with resistance to treatment. In mice, hippocampal ELK-1 overexpression per se produced depressive behaviors; conversely, the selective inhibition of ELK-1 activation prevented depression-like molecular, plasticity and behavioral states induced by stress. Our work stresses the importance of target selectivity for a successful approach for signal-transduction-based antidepressants, singles out ELK-1 as a depression-relevant transducer downstream of ERK and brings proof-of-concept evidence for the druggability of ELK-1.

Optic Pathway Gliomas (OPG) represent 4-6% of brain tumors in children. Treatment of optic pathway gliomas is prompted by neuroradiological evidence of tumor growth, usually associated with progressive visual loss. Despite therapy, approximately 40% will show visual deterioration. Treatment outcome is largely based on the preservation of vision. However, current visual fonction assessment is often unreliable in children with optic pathway gliomas who have limited collaboration. Thus, there is a need for new clinical tools to evaluate visual functions in these children. The_aim of the study was to assess the usefulness of steady-state visual evoked potentials as a tool to assess the integrity of the central and peripheral visual fields of children with optic pathway gliomas.Ten patients with optic pathway gliomas and 33 healthy controls (ages 3 to• 18 years) were tested using steady-state visual evoked potentials. The circular dart-board stimulus consisted of one central circle altemating at 16 reversals/second and one peripheral hoop alternating at 14.4 reversals/second, separated by ahoop of gray space. It was presented Iilonocularly at 30% and 96% contrasts.Results indicated that central signal-to-noise ratios were significantly lower in children with optic pathway gliomas compared to controls. However, no significant group difference was detected in the peripheral visual field.In conclusion, our study shows that steady-state visual evoked potentials could be useful in the clinical assessment and follow up of central visual • field deficits in uncooperative or non-verbal children but seems to have limited usefulness for the evaluation of peripheral visual field defièits. Additional studies are needed to identify • . testing parameters for full visual-field assessment.