Depression

Depression is a syndrome of the whole reward-and-arousal system, not just sadness

The core lesion is a sustained failure of the systems that assign value to experience and mobilise the body to pursue it. Monoaminergic projections (serotonin, noradrenaline, dopamine) from the brainstem tune the limbic and prefrontal circuits that generate mood, drive and the anticipation of reward. When their signalling is chronically dysregulated, the brain stops registering ordinary activities as worthwhile. This is why the two cardinal features are low mood AND anhedonia: the loss of pleasure reflects the reward system itself going offline, not an incidental accompaniment.