 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.During the 1960s and 70s, manic-depression came to refer to just one type of mood disorder (now most commonly known as bipolar disorder) which was distinguished from (unipolar) depression.The terms unipolar and bipolar had been coined by German psychiatrist Karl Kleist.