The multimodal mechanisms of actions of new antidepressants explain that depression may not be caused by the simple deficit of serotonin, but rather can be related to “flooding” 5HT1A autoreceptors in midbrain peri-raphe areas by serotonin itself through the action of glutamate, noradrenaline, and histamine. Here, HTR1A is linked to depressive symptom measurement.