Neuroplasticity in psychiatric disorders: biological mechanisms underlying pathology and treatment

In this thesis, we investigate the role of neuroplasticity in both the pathology (Part 1) and the treatment of psychiatric disorders (Part 2). In Part 1, we examined synaptic density (measured with [¹¹C]UCB-J PET) in schizophrenia spectrum disorder (SSD), in relation to cognitive functioning and other structural brain markers. Patients with SSD and their siblings showed reduced synaptic density compared with controls, whereas only patients exhibited impaired cognitive functioning. In addition, an association between synaptic density and (micro)structural properties of the cortex was observed only in healthy individuals. The siblings further showed an enhanced relationship between synaptic number and white matter structure, which may indicate a potential compensatory mechanism.
In Part 2, we focus on the role of neuroplasticity in the treatment of depression by investigating the mechanisms underlying side effects of electroconvulsive therapy (ECT) and by highlighting, through two systematic reviews, the neuroplastic effects of various antidepressant treatments in humans and animals. Findings from this thesis provide evidence for partially overlapping mechanisms between the rapid-acting antidepressant ketamine and ECT. We also found that conventional antidepressants and ketamine show different patterns of default mode network (DMN) modulation, which are associated with improvements in clinical outcomes. In addition, hippocampal neuroplasticity was associated with undesirable side effects of ECT.
Overall, this thesis highlights that neuroplasticity—at both the synaptic and white matter levels—continuously shapes and reshapes the brain. This dynamic capacity of the adult brain to change and adapt offers opportunities for the treatment of psychiatric disorders.