Research has shown a strong genetic diathesis{psychology/abnormal/intro} for depression. In reviews of twin studies, adoption studies, and family studies, heredity does seem to play a role in predisposing the individual to depression. One study in particular, performed by Kendler and his colleagues, looked at 2000 pairs of female twins. Evidence showed that the individuals at the greatest risk were those with a depressed monozygotic co-twin, followed by those with a dizygotic co-twin with a history of depression, followed by non-identical co-twins with no history of depression. Those with the least risk factor were identical twins with no history of depression. This study also showed that women who had experienced stressful negative events were more likely to develop depression than those who had not. Yet, the effect of this stress, in those who had experienced a negative event, was greater for those individuals who were more genetically liable. In another study that looked at the concordance rate for developing mood disorders between monozygotic and dizygotic twins, Bertelson and his colleagues found, in an index of Danish same-sexed twins in which at least one was diagnosed with a mood disorder, a concordance rate of .69 and of .19 respectively. Furthermore, family studies, such as the one performed by Katz and McGuffin, show that the risk of a proband developing a mood disorder increases as their degree of relatedness to a relative diagnosed with the disorder also increases. All of these studies point to an increased vulnerability for developing unipolar mood disorder in those individuals for whom a relative has also expressed depression. However, these studies also indicate that environment must play a role in the development of depression, since heritability is not one hundred percent, as would be the case if genetics was the only contributing factor.

Other biological factors concerning the etiology of depression focus on the role of neurotransmitters in the brain. One such hypothesis, the monoamine hypothesis, puts forth the theory that depression is caused by the underactivity of monoamines such as dopamaine, seratonin, and norepinephrine. This realization was based partly on the discovery that a group of drugs that inhibit the action of monoamine oxidases, enzymes that break down monoamines, was successful in treating depressed patients. Evidence that further supported this theory was the discovery that the drug reserpine, which was being used to treat hypertension, was leading to the development of major depressive disorder in 15 percent of the subjects. They later found out that reserpine was responsible for depleting levels of norepinephrine and seratonin in nerve terminals. Furthermore, in studies conducted where subjects were given liquid meals either balanced or not balanced with Tripthan, a precursor needed to make seratonin, researchers found that if the meal was not balanced, those subjects reported symptoms of sadness and depression.

However, one of the major problems with these neurobiological theories is that while antidepressants immediately restore the amount of monoamine levels in the brain, their effects on the depressive moods usually take weeks to manifest themselves. This has led to theories proposing that depression is caused by more than simply a deficiency in the amount of neurotransmitters--perhaps by an increase in density and sensitivity of postsynaptic receptors. Animal studies to support this theory, such as the ones performed by McNeal and Cimbolic, have shown that anti-depressants lead to a decrease in the sensitivity and density of these receptors.