5  The network hypothesis of mood disorders

While the neurotrophic hypothesis of mood disorders recognises the importance of BDNF and neurogenesis in explaining how antidepressants work, according to Eero Castre´n of the University of Helsinki, it does not go far enough in recognising the impact and significance of neurogenesis. He suggests that we need a conceptual framework to understand why neurogenesis might be important.

Castre´n (2005) quotes from the Nobel lecture given by Arvid Carlsson, the Swedish scientist who received the prize in 2000 in recognition of his work on the neurotransmitter dopamine: ‘…the brain is not a chemical factory but an extremely complicated survival machine’.

What does this mean? Castre´n argues that to understand how antidepressants work, and what their operation tells us about the brain bases of mood disorders, we need to look beyond the ‘tools’ – molecules such as BDNF – and try to understand what the tools are doing, which, he suggests, is repairing essential functional networks in the brain (Figure 12). A related point he makes is that there may be many different ‘routes’, including psychotherapy and ECT, that set in motion the plasticity processes needed to repair damaged networks (Figure 12c).

Figure 12  The network hypothesis of depression and antidepressant action (a) Networks of neurons process information in a healthy brain; (b) In depression, information processing networks do not function properly, as some neurons are damaged or have died; (c) Antidepressant treatment enhances connectivity in neuron networks: antidepressant medication, electroconvulsive therapy, exercise and psychotherapy can all enhance plasticity which gradually leads to the recovery of connections in damaged neuron networks.

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Part (a) shows a schematic neural network with intact connections between the constituent neurons. In part (b) some of the neurons are shown damaged and so fail to make their connection with a neighbouring neuron. Part (c) shows part of a damaged network on the left and part of an intact network on the right, and between them is a list of four antidepressant treatments that can enhance the plasticity processes needed to remake the neuronal connections and so repair the damaged.

Figure 12  The network hypothesis of depression and antidepressant action (a) Networks of neurons process information in a healthy brain;...

One way of looking at the role of BDNF, then, is that it is not levels of BDNF as such that are important, or even that BDNF promotes neurogenesis. According to the network hypothesis, BDNF’s effects on behaviour will depend on where in the brain it is active, and which networks it therefore affects.