Donald F. Klein’s 7^th comment on Martin M. Katz’s Depression and Drugs

How does the lack of antidepressant effect on normal subjects fit in your schema?

Factor analyses are often misunderstood as producing evidence for discrete groups.  However factors are not discriminants. Yet Katz ties changes in specific neurotransmitters to particular changes in behavioral factors. However, Morilak and Frazer (p. 208), cited by Katz as providing useful background present a more complex model to deal with apparent contradictions:

“For instance, how can drugs that selectively enhance the tonic activity of the serotonergic system, thought to exert a primarily inhibitory influence on behavioral reactivity, produce the same therapeutic effects as drugs that selectively enhance the tonic activity of the noradrenergic system, thought to exert a facilitatory effect on behavioral reactivity? Indeed, if NE facilitates behavioral reactivity and arousal, how can drugs that selectively enhance neurotransmission in this system improve anxiety, at least as they do when it occurs in concert with depression?” Morilak and Frazer present a complex argument involving inhibitory receptors on the afferent neurons to deal with such issues. The apparent value of the rheostat model seems to be predictability, if A goes up, B goes up. Predictability is not evident with this more complex model.

Donald F. Klein

July 9, 2015