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The present work comments on Watt’s Target Article, which argues that focusing on separation distress, a relevant construct from Pankseppian affective neuroscience theory, might help to shed new light on depression. This represents an important new research avenue, because Watt’s recent work shows the difficulties in understanding depression, a devastating state of mind with millions around the globe being afflicted. Several key points of Watt’s work are summarized and reflected on.