**2.3 Mood stabilizers and mechanisms of neuroplasticity**

Lithium and anticonvulsants with mood-stabilizing properties (lamotrigine, valproate) constitute first-line drug treatment for episodes of depression and mania with variable inter-episode remission [27–29]. Whilst different compounds may differentially target specific facets of bipolar disorders, lithium is effective for all phases including acute depression [30]. On the neural level, functional imaging studies consistently point to pre-treatment frontolimbic dysfunction during

cognitive control and emotion-paradigms in bipolar disorder patients [31–33]. Thus, abnormal emotion regulation and impaired cognition might be attributed to interference in cognitive control within medial prefrontal cortex though overactivity in subcortical structures (amygdala, ACC, insula), involved in emotion generation and appraisal. Findings of mood stabilizers-induced neural plasticity yield less consistent results due to methodological limitations that make it difficult to draw firm conclusions. Whilst some studies find no significant effects of pharmacotherapy upon functional measures of cerebral reorganization in bipolar patients [34–41] others reported increased task-related prefrontal cortical activity coupled with normalized subcortical limbic activity during emotional processing [38, 39, 42, 43]. Typically, individuals recruited in these studies are able to tolerate medication withdrawal and washout, and therefore are likely to have a milder form of the disorder. Given that it is not clinically feasible to withdraw all patients with bipolar disorder from medication, individuals with a more severe form of the disorder are likely to be underrepresented in many studies and therefore findings might not be generalizable to the most at-need of new treatments group.
