How Antidepressants Help Create New Connections in Our Brain
Depression has long been conceptualized as a deficiency in certain neurotransmitters. Antidepressants usually work by replenishing the levels of these neurotransmitters. However, it has been recognized that despite the antidepressants rapidly replenishing the levels of the neurotransmitters, symptom reduction requires weeks of treatment with antidepressants. Current knowledge of the pharmacology and biochemical effects is readily available, however less is known about the neurobiological and structural changes that occur while people take antidepressants.
Neuroscientists have shifted their research to the area of neuroplasticity, neurogenesis in adults, and the ability of antidepressants to regulate the expression of genes related to plasticity and resilience. It is still unknown how neuroplasticity affects mood. There are recent findings regarding the effect of antidepressants on neuroplasticity, and specifically findings that suggest that antidepressants reactivate the plasticity in the adult brain such that it is comparable to those of children. This ability might be an essential part of the therapeutic action of antidepressants.
Informational processing including that of emotions, and cognitions is based on neuronal networks. Neurotransmitters serve to mediate informational transfer between neurons; however, it is the actual wiring of the neurons, and not the level of the chemical messengers that contributes to information reprocessing. Neuroplasticity mediates structural and functional changes within these networks.
There is a growing understanding that mood disorders are associated with neuronal network structural abnormalities. Hubel and Wiesel (1960) established that sensory experiences shape the way the brain develops structurally. They also showed that the degree to which the brain is capable of changing is age dependent, with the highest levels of plasticity occurring during critical periods of development in early life. After these critical periods plasticity is limited to strengthening, or weakening of existing synapses. The strengthening and weakening of synaptic strength is modified by external experiences such as stress, depression and antidepressant drugs.
Recent studies suggest that recovery from depression does not simply involve an increase in the levels of neurotransmitters, rather a structural change in neuronal networks, which facilitates an increased ability to adapt to the environment. This contributes to the understanding that the initial chemical effects of antidepressants begin a period in which neuronal networks readjust structurally to better characterize the external and internal environment. This process takes weeks, and is consistent with the delay in symptom reduction one experiences when commencing antidepressants. In studies utilizing rats it was demonstrated that the administration of Fluoxetine reactivated brain plasticity so that a neuronal network that was miswired during development can be reorganized. Recovery of the network was only achieved when it was combined with supportive rehabilitation services. Another factor that increased neuronal plasticity was moving the rats from their normal habitat to an enriched environment. Similarly, it has been found that patients with depression treated with placebo show a noticeable response, which in cases of mild depression, is comparable to the effect of antidepressants. In these studies the placebo can be thought about as an enriched environment.
The initial studies done with rats were able to demonstrate increased neuroplasticity in the visual cortex. Later studies demonstrated that the increased neuroplasticity activated by the commencement of Fluoxetine combined with extinction training similar to Flooding in humans, produced long lasting changes in mood related neuronal networks.
Further research is needed in order to conclude that the same neuroplasticity activated in animals is indeed activated in humans, and further research into the mechanism of other effective antidepressants such as ketamine. Preliminary studies suggest that antidepressants do activate neuroplasticity in adult human brains as observed by an increased neuroplasticity in the adult visual cortex of both depressed and healthy controls, prior to providing them with sertraline hydrochloride.
These findings have important clinical implications. First, this hypothesis might support the studies that suggest that combination of antidepressants and psychotherapy such as CBT, or group treatment provide long-term effects and a reduction in depressive symptoms. This also has implications for patients that have been found to be treatment resistant. A third of patients taking antidepressants have been found to be treatment resistant. It is possible that these patients have insufficient environmental support, and are lacking interactions to support the recovery of the neuronal network. These findings are informative for treatment planning, and suggest that patients should receive psychological treatment or other types of psychological support from the commencement of medication treatment in order to support, the effects of neuroplasticity and recovery. A second important implication of these findings is that antidepressants might be helpful for a variety of conditions in which there might be a benefit from increased neuronal plasticity such as OCD, PTSD, and anxiety.