Staging and Neuroprogression in Bipolar Disorder

Abstract

The apparently progressive nature of a considerable proportion of cases of bipolar disorder (BD) has been acknowledged in recently proposed clinical staging models. This has been part of an attempt to facilitate and refine diagnosis, treatment selection, and establish a prognosis. The study of the progressive nature of some cases of BD has given raise to the hypothesis of neuroprogression, which postulates that different stages of BD are associated with distinct neurobiological underpinnings. Given that BD may be intimately associated with chronic stress response and coping mechanisms over the course of illness, we propose that cellular resilience mechanisms may play a key role in the neuroprogression in BD. In the present study, we review neuroanatomical evidence of the progression that occurs in many cases of BD, as well as cellular resilience mechanisms and peripheral biomarkers associated with distinct stages of this disorder. In summary, cellular resilience mechanisms seem to be less efficient at later stages of BD, especially mitochondrial and endoplasmic reticulum-related responses to stress. These insights may help in developing staging models of BD, with a special emphasis on the search for biomarkers associated with illness progression.

Biomarkers and staging of bipolar disorder: a systematic review

“…6,8,[11][12][13] Moreover, changes in cognitive functions are more marked in advanced stages of the disease than in controls and in patients in the initial phases of this psychiatric disorder. 8 Recent studies also showed that cognitive dysfunction and functional deterioration persist even during the euthymic periods in the advanced stages of the disease.…”

“…5 A growing body of evidence suggests that BP is a progressive disease. [6][7][8] In 1899 Emil Kraepelin found that the intervals between mood episodes become successively shorter as the number of previous episodes increases. The same author described that, after a certain number of recurrences, episodes tend to occur more spontaneously, in contrast with initial episodes, which are usually triggered by psychosocial stress factors.…”

Early stages of bipolar disorder: characterization and strategies for early intervention

“…11,12 The clinical progression described above is hypothesized to be subserved by neurobiological changes, the so-called neuroprogression. [13][14][15] This hypothesis is based on observations that brain morphology alterations, such as reductions in volume and gray matter and enlargement of ventricles, are more pronounced in chronic patients than in individuals with fewer episodes. Similarly, evidence indicates a different profile in peripheral biomarkers linked to BD pathophysiology and a wider range of abnormalities in such biomarkers in these patients, 16 including differences in levels of neurotrophins, specifically the brain-derived neurotrophic factor, and inflammatory and oxidative stress markers.…”

Bipolar bozuklukta allostaz ve allostatik yükü yeniden değerlendirmek

“…Accumulation of such toxicity becomes more evident at later stages of illness (33)(34)(35)(36)(37)(38), causing less efficient cellular resilience mechanisms that may be leading to a pathological reorganization between different brain areas (39). This rewiring of the brain within the context of clinical and cognitive deterioration is called "neuroprogression".…”

“…This rewiring of the brain within the context of clinical and cognitive deterioration is called "neuroprogression". Neuroprogression is suggested to be associated with the impaired resilience to stress in patients with BD (39). In sum, it has been proposed that mood episodes generate an extra load on the allostasis that is responsible for the illness progression (15).…”