BDNF, depression, windows of plasticity, and resilience
While there are many potential mediators of resilience, we will focus on the potential role of BDNF in this short review. In some views, depression may be a consequence of inadequate resilience to psychological stressors. Numerous studies suggest that depression is more prevalent in individuals who have had adverse early life experiences [27]. Importantly, low BDNF may be a key feature of the depressive state, and elevation of BDNF by diverse treatments ranging from antidepressant drugs, such as fluoxetine, to regular physical activity may be a key feature of treatment [28]. A growing view is that such treatments may “reopen” windows of plasticity, and effectively provide a means to engage plasticity systems that can help ameliorate depressive moods by altering the neural pathways that underlie them. Such drugs may also increase plasticity more generally, as the recently reported ability of fluoxetine to enhance recovery from stroke suggests [29]. However, a key aspect of this new view [30] is that, while such drugs open these “windows of opportunity”, the effects will only be capitalized on by a positive behavioral intervention, e.g. behavioral therapy in the case of depression or on intensive physiotherapy to promote neuroplasticity to counteract the effects of a stroke.
This is consistent with animal models that show that ocular dominance imbalance from early monocular deprivation can be reversed by patterned light exposure in adulthood that can be facilitated by fluoxetine, on the one hand, [31] and food restriction (or, alternatively, intermittent glucocorticoid treatment), on the other hand [32], in which inhibitory neuronal activity plays a key role [33]. Investigations of underlying mechanisms for the re-establishment of a new window of plasticity are focusing on the balance between excitatory and inhibitory transmission and molecules that put the “brakes” on such plasticity [34].
As to the role of glucocorticoids, there is a biphasic relationship to plasticity, as shown by studies in which the turnover of dendritic spines in the cortex is inhibited when hypothalamic pituitary adrenal (HPA) function is suppressed by a small dose of dexamethasone and restored in a biphasic manner by increasing replacement levels of corticosterone [35]. This may be related to the finding that corticoids acutely and ligand-independently activate the trkB receptor [36] and that chronic corticoid treatment has the opposite effect [37].