The term "unipolar" (along with the related term "bipolar") was coined by the neurologist and psychiatrist Karl Kleist, and subsequently used by his disciples Edda Neele and Karl Leonhard.
In the mid-20th century, researchers theorized that depression was caused by a chemical imbalance in neurotransmitters in the brain, a theory based on observations made in the 1950s of the effects of reserpine and isoniazid in altering monoamine neurotransmitter levels and affecting depressive symptoms.