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could help to understand the relationship between long illness duration and repeated affective episodes
inflammation and mood episodes. This relationship rather than being a core feature of the pathophysiology
can be causal (thus preceding and predicting the of BD at onset.
development of a mood disorder), merely associated
with the disease or a consequence of a long lasting Reasons of weakness and inconsistency across the
illness. studies are diverse and include heterogeneity of the
samples (age and considered BD phases, concurrent
Only three studies [29,35,37] examined BDNF and use of drugs, substance abuse, comorbidity with
inflammatory markers in small populations of pediatric other medical illnesses, effect of other psychiatry
BD, thus the reported findings are mostly preliminary conditions, especially anxiety related disorders),
and not replicated. Six additional studies examined small to modest sample sizes and differences in
the role of oxidative stress, inflammatory cytokines studied biological pathways. Also, it is worth to
and BDNF in the pathophysiology of early‑onset BD underscore that peripheral change in biological
during adult age. [10,36,38‑41] markers might not always correspond to comparable
changes of the same markers in the central nervous
Concordant findings showed that inflammatory system.
markers are increased since the earlier
stages of BD with: (1) increased TNF‑α gene CONCLUSION
expression in adolescent BD showing aggressive
behaviors; [35] (2) increased TNF‑α levels in young There are preliminary findings indicating that a potential
adults with bipolar depression; [36] (3) increased relationship exists between inflammatory process and
TNF‑α levels since the earlier stages of BD; [10] and juvenile BD, but evidences are insufficient to support
(4) positive correlations between TNF‑α levels and the causality. Adequately powered and prospective
length of bipolar illness. [10] Also, increased levels of studies on high risk population as well as studies
hsCRP have been detected in juvenile BD patients examining the relationship between mood‑stabilizing
during manic and mixed episodes. [29] treatment and changes in inflammatory, oxidative
markers and neurotrophins levels are warranted to
A positive correlation was found between decreased understand their role in the pathogenesis of BD.
levels of peripheral BDNF and a manic, depressive or
mixed episode in juvenile and young adult BD, [36,37] Financial support and sponsorship
even though such findings have not been always It was supported by the Research Fellowship from
replicated. [10,29] In fact, some authors have suggested Sapienza University of Rome to Dr. Giulia Serra.
that changes in peripheral levels of BDNF might occur
only during the late stage of BD and might reflect the Conflicts of interest
neurodegeneration of late stage mood disorders. [10] There are no conflicts of interest.
Indeed, recent preclinical and clinical evidences
suggested that the excitotoxicity due to an excessive REFERENCES
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