Adult neuroplasticity: A new “cure” for major depression?

Abstract

Neuroplasticity involves synaptic reorganization (Box 1) in response to environmental stressors or rewards and is thought to underlie our ability to adjust, learn and remember. 7 However, in mental illness, it is thought that maladaptive plasticity occurs, resulting in persistence of the depressive symptoms, such as rumination, anhedonia and others. 8 By harnessing corrective neuroplasticity (Box 2), it may be possible to reprogram the maladaptive behaviour and produce long-lasting remission. This editorial presents evidence that both pharmacological and brain stimulation antidepressant approaches may act by inducing corrective neuroplasticity to mediate remission. Increasingly, antidepressant effects on neuroplasticity are shown to correlate with behavioural improvement, both in humans 18 and in animal models, 19 raising the possibility that neuroplasticity could provide a new avenue for depression research. However, learning how to harness this capacity to enhance recovery remains a challenge.

Fluoxetine-induced recovery of serotonin and norepinephrine projections in a mouse model of post-stroke depression

“…These results implicate the neuroplasticity of 5-HT projections in mediating effective antidepressant treatments. In combination with the ability of FLX to enhance neuroplasticity of post-synaptic cortical neurons 8 , 69 – 71 , these presynaptic actions on 5-HT projections may lead to functional 5-HT synapses and restore behavioral and cognitive functions.…”

“…In major depression and mild cognitive impairment, deficits in gray matter volume and 5-HT innervation are seen in the PFC 82 , 83 , and reduced cortical thickness has been associated with 5-HT genetic markers 84 , 85 . The finding that effective treatment of major depression is associated with a reversal of reduced cortical thickness 86 and increased connectivity to the 5-HT system 87 , 88 suggests that SSRI-induced axonal neuroplasticity may be an important mechanism in its antidepressant actions in humans 8 , 71 .…”

Immunological Interfaces: The COVID-19 Pandemic and Depression

“…Neuroplasticity describes neural synaptic reorganization in response to environmental input. It is thought to form the basis for memory and learning (68). Impaired neuroplasticity is implicated in the pathogenesis of depression ( 69), a mechanism supported by alterations in brain functional connectivity (70) as well as loss of synapse-related genes and synapses in postmortem brain tissue of patients with depression (71).…”

How do serotonergic psychedelics treat depression: The potential role of neuroplasticity

“…However, the neuroplasticity model of depression suggests that maladaptive plasticity can also lead to problems, such as those that occur in major depressive disorder (MDD). Antidepressants may work in part by harnessing the power of neuroplasticity to change brain circuits driving maladaptive cognitions and behaviors and thereby improve symptoms[ 5 ]. This neuroplasticity-based theory of depression and antidepressant action may also provide an explanatory model for how the novel antidepressant, ketamine, exerts its antidepressant effects.…”