Cortical Magnetic Resonance Imaging Findings in Familial Pediatric Bipolar Disorder

Synergistic Neuroprotective Effects of Lithium and Valproic Acid or Other Histone Deacetylase Inhibitors in Neurons: Roles of Glycogen Synthase Kinase-3 Inhibition

“…Structural imaging studies showed a reduction in gray matter volume in orbital and medial prefrontal cortices, ventral striatum, and hippocampus as well as enlargement of the third ventricle in bipolar patients (for review, see Manji et al, 2003;Chuang and Manji, 2007). Protracted treatments of bipolar patients with lithium or VPA have been found to suppress the loss of gray matter volume in the prefrontal cortex and amygdala compared with patients receiving no such treatment (Drevets, 2001;Chang et al, 2005). These and other studies suggest that neuroprotective and neurotrophic effects of mood stabilizers, most likely through GSK-3 inhibition, enhance cellular resilience and plasticity and, in turn, contribute to their clinical efficacy (for review, see Manji et al, 2001; Bachmann et al, Figure 8.…”

“…Long-term lithium treatment increases total gray matter content (Moore et al, 2000a) and enhances levels of N-acetyl-aspartate, a marker of neuronal viability, in the brain of bipolar patients (Moore et al, 2000b). Moreover, bipolar subjects with past lithium or VPA exposure tend to have greater amygdalar gray volume than control patients without such an exposure (Chang et al, 2005). Interestingly, the loss of the subgenual prefrontal cortex volume found in bipolar patients was essentially suppressed in patients receiving protracted lithium or VPA (Drevets, 2001).…”

A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder

“…These have revealed structural alterations in both cortical 197 and subcortical 161,[198][199][200] regions. Studies in adolescent and first-episode BD 198,199 as well as one longitudinal study of adolescents 161 demonstrate smaller amygdalae and smaller 200,201 or normal-sized hippocampi 198,199 in adolescent BD, which differ from the above findings of enlarged amygdalae in adults.…”

Thalamofrontal neurodevelopment in new-onset pediatric idiopathic generalized epilepsy

“…There is literature suggesting that AEDs in humans can negatively impact gray matter structure, although these reports come from outside the epilepsy literature. 30,31 Several animal studies suggest AEDs affect cell proliferation, differentiation, and migration, and other processes such as myelination which may cause neurodegenerative changes in regions such as the thalamus. 32 It is unknown if these findings translate to individuals beginning AED treatment in late childhood and adolescence, as there is no longitudinal literature indicating AED-induced gray matter loss in children with postnatal only exposure to AEDs.…”