Table 2. Predictions made by the neuroplasticity and cognitive neuropsychological theories.
| Neuroplasticity theory | Neuropsychological theory | |
|---|---|---|
| Target development | Novel agents should target neural plasticity that reverses synaptic deficits in prefrontal cortex and hippocampus caused by stress | Novel agents should target neural plasticity or transmitter systems in amygdala and cortex that control emotional processing |
| Speeding up of antidepressant effects | Faster or more direct actions on neural plasticity; environmental enrichment to facilitate effects of plasticity | Enhance the translation of emotional processing change into clinical change by environmental enhancement and targeted psychological treatments |
| Example reasons for non-response | Insufficient neural architecture to support plasticity change; insufficient effect of drug on plasticity | Entrenched emotional processing response, which is difficult to shift; toxic environment or reduced environmental engagement |
| Prediction of individual drug response | Measures of plasticity-induced neurotrophic and synaptic markers should predict treatment success | Early change in emotional processing should predict later clinical change |
| Exploration of the relationship between the two theories | Restriction of plasticity change should reduce the effect of agents on emotional bias in animal models | Blockade of the expression of negative bias change should reduce the plasticity changes induced by antidepressant agents |
| Combination approaches | Agents that target neural plasticity combined with emotional processing change will have effects greater than either target in isolation; in particular, effects of ketamine will be sustained when combined with agents that shift negative biases in emotional processing | Agents that target neural plasticity combined with emotional processing change will have effects greater than either target in isolation; in particular, effects of ketamine will be sustained when combined with agents that shift negative biases in emotional processing |
These predictions do not necessarily represent competing views but rather different perspectives, levels of analysis, and methods that can be synergistic or overlapping.