The role of hippocampus in the pathophysiology of bipolar disorder

Abstract

Bipolar disorder (BD) is thought to be associated with abnormalities within discrete brain regions associated with emotional regulation, particularly in fronto-limbic-subcortical circuits. Several reviews have addressed the involvement of the prefrontal cortex in the pathophysiology of BD, whereas little attention has been given to the role of the hippocampus. This study critically reviews data from brain imaging, postmortem, neuropsychological, and preclinical studies, which suggested hippocampal abnormalities in BD. Most of the structural brain imaging studies did not find changes in hippocampal volume in BD, although a few studies suggested that anatomical changes might be restricted to the psychotic, pediatric, or unmedicated BD subgroups. Functional imaging studies showed abnormal brain activation in the hippocampus and its closely related regions during emotional, attentional, and memory tasks. This is consistent with neuropsychological findings that revealed a wide range of cognitive disturbances during acute mood episodes and a significant impairment in declarative memory during remission. Postmortem studies indicate abnormal glutamate and GABA transmission in the hippocampus of BD patients, whereas data from preclinical studies suggest that the regulation of hippocampal plasticity and survival might be associated with the therapeutic effects of mood stabilizers. In conclusion, the available evidence suggests that the hippocampus plays an important role in the pathophysiology of BD.

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

“…TLR2, but not TLR4, has also been implicated in the perpetuation of inflammatory responses in the CNS after pro-inflammatory stimulation of astrocytes [70] and involved in hippocampal neurogenesis as mice lacking TLR2 displayed impaired hippocampal and neuronal differentiation, which was not observed for TLR4 [71]. These observations could be related to the TLR2 specificity of our findings especially as hippocampal alterations have been repeatedly reported in adults with a history of childhood traumatic experiences and are suggested to be involved in the pathophysiology of BD [72][73][74].…”

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

“…A postmortem study demonstrated reduced pyramidal cell size in the hippocampus of BD patients compared with healthy control subjects (Liu et al, 2007). Most previous in vivo studies also showed no difference in hippocampal volumes between BD patients and healthy subjects (Frey et al, 2007a), although a few studies have shown smaller hippocampal volumes in BD patients (Bearden et al, 2007;Frazier et al, 2005). Lithium and valproate, primary mood stabilizers for the pharmacological treatment of BD patients, increase BDNF concentration in the rat hippocampus .…”

Psicoterapia psicodinâmica e tratamento biológico com fluoxetina: comparação de resposta cognitiva em pacientes deprimidos

“…Como verificado no presente trabalho, houve melhora em funções cognitivas associadas a circuitos neurocognitivos variados, incluindo o córtex pré-frontal, o hipocampo e o circuito límbico-fronto-estriatal. Alguns estudos já haviam relacionado essas áreas ao humor deprimido (Frey et al, 2007;Porter et al, 2007).…”