How is neuroplasticity affected in depression?
Updated: Feb 2, 2021
Key take home points:
Neuroplasticity is the brains ability to adapt and grow as we learn, experience and adapt.
Structural neuroplasticity involves volumetric changes to brain connections and functional neuroplasticity involves alterations to neuronal function and synaptic strength.
Neuroplasticity is altered in the hippocampus, pre-frontal cortex and amygdala of depressed people to encourage negative, unhealthy and maladaptive pathways.
The exact mechanism to link neuroplasticity and depression is unknown however research suggests that stress is involved.
Anti-depressants may work through exerting an effect on neuroplasticity. Both SSRI and psychedelic anti-depressants have been suggested to involve neuroplasticity in their mechanism of action.
What is neuroplasticity?
Neuroplasticity is the ability of the brain to change continuously throughout an individual’s life. The aim of neuroplasticity is to optimise and shape the brains neuronal networks as we experience, learn and adapt [1].
There are two types of neuroplasticity: structural and functional. Structural neuroplasticity refers to the ability of the brain to change its neuronal connections. Functional neuroplasticity is the brains ability to alter and adapt the function of neurons and synapses.
How is neuroplasticity altered in depression?
Scientists believe that neuroplasticity is disrupted in depression. It is thought that depression can cause damage to the brain through encouraging unhealthy and maladaptive pathways and discouraging the healthy and adaptive pathways associated with neuroplasticity [2]. This can result in the persistence of depressive symptoms [3].
It is unknown exactly how neuroplasticity and depression link together. The changes in plasticity may be arising through long-term increases and decreases in synaptic strength [4].
Changes to structural and functional neuroplasticity have been seen in the hippocampus, prefrontal cortex and the amygdala in depressed people’s brains [5]. These brain regions make up the limbic system and are involved in emotion, memories and arousal.
Some treatments for depression may be able to halt or reverse the damage to neuroplasticity caused by depression [2] and it has been suggested that some anti-depressants exert their effects through regulating neuroplasticity [5].
Neuroplasticity in the hippocampus
The hippocampus is involved in the formation of new memories and is associated with learning and emotions. Depression is associated with alterations in synaptic plasticity within the hippocampus [5]. Changes to the volume of neurons also occurs in the hippocampus of depressed people [6-8]. Reduced hippocampal volume is also seen in the brains of people who have recovered from depression [8].
Neuroplasticity in the prefrontal cortex
The prefrontal cortex (PFC) is a central regulator of thinking and behaviour. It can be split into two regions: the ventromedial PFC (vmPFC) and the dorsolateral PFC (dlPFC). The vmPFC is involved in regulation of affection and generation of negative emotion and the dlPFC is involved in mediating cognitive function. In depression, the vmPFC is hyperactive and the dlPFC is less active due to reduced neuron number and plasticity. The synaptic plasticity of neurons in the PFC is also reduced in depression [5].
Neuroplasticity in the amygdala
The amygdala is thought to play a key role in processing emotions. In depression, scientists believe there is reduced functional connectivity of neurons in the amygdala [5]. The networks involved in negative emotions are increased and those involved in positive emotions are decreased [9]. Research has also demonstrated changes in the volume of grey matter associated with the changes in the positive and negative networks [5], as well as altered synaptic plasticity.
What causes changes to neuroplasticity?
The limbic system is very susceptible to stress and depression. Changes in neuroplasticity induced by stress or other negative stimuli, including pain or cognitive impairment, can play a significant role in the development of depression [5]. Chronic stress can replicate the impaired neuroplasticity [10-12] seen in models of depression.
Neuroplasticity and serotonin
Changes in the serotonin system have been implicated in depression (see previous post). Most classical anti-depressants target the reuptake of serotonin to increase serotonin signals throughout the brain and are called selective serotonin reuptake inhibitors (SSRIs).
In the PFC and hippocampus of depressed people, reductions in serotonin innervation have been associated with reductions in the volume of neurons [13], suggesting a role for serotonin in neuroplasticity changes occurring in depression. Furthermore, activation of serotonin neurons via SSRIs treatment can trigger neuroplasticity of the serotonin system and increase the volume of neurons [14, 15].
Neuroplasticity and ketamine
Ketamine is a psychedelic drug that has been shown to produce rapid improvements in treatment-resistant depressive disorder [16, 17]. Ketamine acts as a brain stimulator to increase glutamatergic activity and trigger the formation of new dendrites on neurons to improve synaptic strength [18]. In rat models, ketamine has been shown to induce neuroplasticity and behavioural improvements [19]. This suggests a role for neuroplasticity in the mechanism of ketamine, and potentially other psychedelics.
References
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