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Su et al. [36] investigated pro‑inflammatory cytokines significantly decreased in patients with late‑stage
levels in a cohort of young males suffering from reactive BD. The decrease in BDNF levels appeared to be
depression or major depression, or bipolar depression proportional to the length of illness and BDNF levels
compared to matched sample of healthy control were negatively correlated to the number of mood
subjects. They found significantly higher levels of episodes. [10]
TNF‑α and significantly lower levels of adiponectin in
depressed youths compared to healthy controls, with Oxidative stress
no difference in both TNF‑α and adiponectin levels Two studies about the measurement of glutathione (GSH)
between depressive subtypes. [36] No difference was concentrations in young adult patients with BD
found in IL‑6 and hsCRP levels between depressed compared to healthy subjects suggested that there
and healthy subjects and between different subtypes was no difference in GSH level in the ACC between
of depression. [36] Consistently with these findings patients and controls. [38,39] They reported that GSH
supporting early changes in pro‑inflammatory cytokine levels were not correlated with depressive and manic
levels during the psychopathological development of episode severity [38] and were not significantly different
BD, Kauer‑Sant’Anna et al. [10] found that TNF‑α and between unmedicated and medicated subjects. [39] Also,
IL‑6 levels were already significantly increased in they found that GSH levels were decreased in bipolar
early‑stage BD patients compared to healthy controls subjects with high levels of alcohol intake. [39]
and continued to be higher in BD subjects than controls
also in the late‑stage of the disease. Additionally, they Magalhaes et al. [40] suggested that young adults with
found a positive correlation between TNF‑α levels and a lifetime history of hypomania had higher levels
length of illness. [10] Conversely, the anti‑inflammatory of oxidative damage to proteins as measured by the
IL‑10 levels were increased in the early stage of BD determination of carbonyl groups [protein carbonyl
but not in the late stage of BD. [10] content (PCC)] when compared to healthy young
adults. High serum PCC levels were associated with
BDNF a current manic episode, but not with a current
Pandey et al. [37] compared gene expression and protein depressive episode. Conversely, the levels of lipid
levels of BDNF in a sample of 26 manic or mixed peroxidation as measured using the TBARS method did
BD adolescents before and after mood‑stabilizing not significantly differ between mood disorder subjects
treatment with a sample of 21 matched healthy and healthy controls and did not correlate with manic
controls. They measured BDNF mRNA levels in or depressive mood state. [40]
lymphocytes of BD subjects before and after treatment
and in healthy controls and BDNF protein levels in A significant gender‑related difference in oxidative
platelets of drug‑free BD and healthy subjects. They stress parameters was reported by the same group [41]
found that (1) BDNF mRNA levels in lymphocytes showing higher PCC and lower uric acid levels in
and BDNF protein levels in platelets of drug‑free females when compared to males. No association
subjects with BD were significantly lower compared was found between oxidative stress parameters and
to those of healthy controls; (2) long‑term treatment bipolar versus major depressive disorder in both
with mood‑stabilizing drugs significantly increased the genders. [41]
levels of BDNF mRNA in the lymphocytes of subjects
with BD; and that (3) BDNF mRNA level of BD patients DISCUSSION
during the 8th week of treatment was comparable to
that of healthy control subjects. [37] The study of inflammatory factors in chronic psychiatric
conditions is a relatively new field of research that has
Measurements of BDNF peripheral levels in a sample of already highlighted several important areas of focus in
young adult males diagnosed with bipolar depression populations of adult BD patients. [1,3]
showed that BDNF levels were significantly lower in
depressed subjects than in healthy controls. [36] Our review provides a summary of preliminary findings
about the link between inflammatory processes,
These finding were not replicated in a later study [29] decreased neurotrophins, increased oxidative stress and
reporting that BDNF levels in a sample of BD juvenile or young adult age BD. Two different lines of
adolescents were not correlated with any illness research have been pursued in this field, one regarding
phase (depressive or manic), but was significantly early onset (pediatric) of BD and the other on the effects
and inversely associated with IL‑6 levels. Consistently of course variables (duration of illness, number of
with this last observation, Kauer‑Sant’Anna et al. [10] episodes, hospitalizations) on changes in inflammatory
found that BDNF levels were similar between patients markers, neurotrophins and markers of oxidative stress.
with early stage BD and matched controls but were Studying inflammatory mechanisms in pediatric BD

248 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015