Biological hypotheses and biomarkers of bipolar disorder

Abstract

The most common mood disorders are major depressive disorders and bipolar disorders (BD). The pathophysiology of BD is complex, multifactorial, and not fully understood. Creation of new hypotheses in the field gives impetus for studies and for finding new biomarkers for BD. Conversely, new biomarkers facilitate not only diagnosis of a disorder and monitoring of biological effects of treatment, but also formulation of new hypotheses about the causes and pathophysiology of the BD. BD is characterized by multiple associations between disturbed brain development, neuroplasticity, and chronobiology, caused by: genetic and environmental factors; defects in apoptotic, immune-inflammatory, neurotransmitter, neurotrophin, and calcium-signaling pathways; oxidative and nitrosative stress; cellular bioenergetics; and membrane or vesicular transport. Current biological hypotheses of BD are summarized, including related pathophysiological processes and key biomarkers, which have been associated with changes in genetics, systems of neurotransmitter and neurotrophic factors, neuroinflammation, autoimmunity, cytokines, stress axis activity, chronobiology, oxidative stress, and mitochondrial dysfunctions. Here we also discuss the therapeutic hypotheses and mechanisms of the switch between depressive and manic state.

Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies

“…Monoamine metabolites, dexamethasone suppression test, BDNF, oxidative stress markers, immunological markers (interleukin‐6, tumor necrosis factor‐α, etc. ), and gene‐expression markers have drawn attention in biomarker studies for BD …”

“…The dexamethasone suppression test is altered, but it is not a specific test for BD and has limited clinical utility.…”

Brain morphologic changes in early stages of psychosis: Implications for clinical application and early intervention

“…On the other hand, while gray matter changes of the STG and insula in first‐episode schizophrenia seem to be rather disease‐specific among various psychotic disorders (e.g., affective psychosis and schizophreniform disorder), gross morphologic features, such as the size of midline structures and olfactory sulcus depth did not differ between schizophrenia and other psychosis subgroups. Further, patients with other neuropsychiatric disorders, such as major depression, bipolar disorder, and borderline personality disorder, are likely to exhibit similar gross morphologic and gray matter changes (e.g., frontal and temporo‐limbic atrophy) to those reported in schizophrenia patients. Thus, the MRI findings in schizophrenia are supposed to include both those specific to schizophrenia and those more generally observed across various neuropsychiatric disorders.…”

Translocator Protein-18 kDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases

“…Although the pathophysiology of this severe mental illness remains to be elucidated, a large body of literature suggests that several pathophysiological processes may sequentially and/or concurrently occur in BD, as well as corticolimbic control circuits deterioration, monoaminergic neurotransmission imbalance or microglia homeostasis disruption (for review, see Sigitova et al, 2016 [154]). Among these, hippocampal neuroinflammation, assessed by enhanced 11 C-PK11195 binding compared to healthy subjects [155], could echo the change in the cytokines pattern’s profile (TNF, IL-1, IL-2 and IL-6) of BD-I patients [156] (Table 6).…”