Reid & Stewart (Reference Reid and Stewart2001) review evidence for a neurobiological basis of depression and it is suggested that brain plasticity plays a major role. These plasticity changes involve neuronal atrophy, neurogenesis, dendrite involution and formation, and long-term potentiation (LTP). Electroconvulsive therapy (ECT) and antidepressants enhance LTP and, as Reid & Stewart imply, the benefits (and adverse effects) of such treatments may be due to an enhancement or saturation of LTP. We question whether abnormal LTP per se is a critical neurobiological path to the changes seen in depression. We support the view that alterations in structural plasticity, as opposed to LTP, are more critical. Antidepressants, ECT, depression and stress can all modulate neuronal structure and LTP has been shown to be abnormal in models of depression and stress, but it does not follow that abnormal LTP is a prerequisite for these states, even though LTP is accepted to be important in, for example, associative learning.

In studies where LTP has been shown to alter neuronal structure, the increase in synaptic efficacy (assayed electrophysiologically) occurs within seconds to minutes but the earliest detected structural changes take at least 20 minutes (Reference Yuste and BonhoefferYuste & Bonhoeffer, 2001). This time frame also does not correlate with the time required for the effects of antidepressant treatment (including ECT) — structural changes correlate better. Furthermore, although LTP is associated with morphological changes, these do not necessarily contribute to the potentiation (Reference Yuste and BonhoefferYuste & Bonhoeffer, 2001). This casts doubt on the notion that the alterations in LTP are critical to the pathophysiological mechanism. We support the notion that the primary pathology is due to maladaptive neuronal structural change (Reference Vaidya and DumanVaidya & Duman, 2001). The most likely reason why LTP can be affected by stress and depression, or by treatments for depression, is because such stimuli activate neuronal molecular signalling pathways. These pathways overlap with each other and with the signalling pathways that lead to dendritic structural changes.