Neurobiological trait abnormalities in bipolar disorder

Abstract

Dissecting trait neurobiological abnormalities in bipolar disorder (BD) from those characterizing episodes of mood disturbance will help elucidate the aetiopathogenesis of the illness. This selective review highlights the immunological, neuroendocrinological, molecular biological and neuroimaging abnormalities characteristic of BD, with a focus on those likely to reflect trait abnormalities by virtue of their presence in euthymic patients or in unaffected relatives of patients at high genetic liability for illness. Trait neurobiological abnormalities of BD include heightened pro-inflammatory function and hypothalamic-pituitary-adrenal axis dysfunction. Dysfunction in the intracellular signal transduction pathway is indicated by elevated protein kinase A activity and altered intracellular calcium signalling. Consistent neuroimaging abnormalities include the presence of ventricular enlargement and white matter abnormalities in patients with BD, which may represent intermediate phenotypes of illness. In addition, spectroscopy studies indicate reduced prefrontal cerebral N-acetylaspartate and phosphomonoester concentrations. Functional neuroimaging studies of euthymic patients implicate inherently impaired neural networks subserving emotional regulation, including anterior limbic, ventral and dorsal prefrontal regions. Despite heterogeneous samples and conflicting findings pervading the literature, there is accumulating evidence for the existence of neurobiological trait abnormalities in BD at various scales of investigation. The aetiopathogenesis of BD will be better elucidated by future clinical research studies, which investigate larger and more homogenous samples and employ a longitudinal design to dissect neurobiological abnormalities that are underlying traits of the illness from those related to episodes of mood exacerbation or pharmacological treatment.

Comorbidades clínicas e psiquiátricas em pacientes com transtorno bipolar do tipo I

“…Pesquisas têm demonstrado que a desregulação do humor e do apetite compartilha alguns substratos neurobiológicos 24 . Dados de neuroimagem, por exemplo, mostram que há sobreposição dos circuitos neurais ligados à regulação do humor e do comportamento alimentar, como as conexões entre a amígdala e o córtex pré-frontal 25,26 . Além disso, a hiperatividade persistente do eixo hipotálamo-hipófise-adrenal em pacientes bipolares pode estar relacionada a elevação da pressão arterial, aumento de resistência à insulina e dislipidemia 27,28 .…”

Neural ECM in addiction, schizophrenia, and mood disorder

“…In bipolar disorder, depressive symptoms alternate with periods of mania, characterized by elevated mood and energy, and sometimes psychosis. The neurobiology underlying bipolar disorder partly overlaps with that of MDD and is thought to affect similar neural processes and circuitry, such as synaptic plasticity in the PFC and other areas that regulate cognition (Langan and Mcdonald, 2009;Martinowich et al, 2009). Bipolar disorder has been associated with altered morphologies and densities of interneurons and pyramidal cells in the hippocampus and PFC and has recently been proposed as a progressive neurodevelopmental disorder (Martinowich et al, 2009;Savitz et al, 2014).…”

Cytokines in Bipolar Disorder: Paving the Way for Neuroprogression

“…TNF- α acts on TNFR1 being capable of inducing neuronal cell death through the activation of caspases and apoptotic machinery [80, 81], TNF-mediated process might contribute to the volumetric reduction, and hypoactivation of frontal lobes in BD [82, 83] which are associated with disinhibition of limbic structures [84]. This corticolimbic dysfunction may underlie the emotional dysregulation and cognitive impairment associated with BD.…”

“…One of the possible pathways is the persistent activation of the HPA axis. Medical conditions, including cardiovascular and endocrine diseases, can cause and are exacerbated by chronic stress and HPA axis activation [83, 84, 87–89]. HPA axis activity presents a major role in the regulation of immune response.…”