br Materials and methods br Results
Materials and methods
Discussion Our study assessed the cytokine and chemokine changes associated with first onset PP as compared to HP and HNP groups. In the monocytes/ macrophages/ dendritic 5-ht3 panel, IL-6 levels were found to be significantly elevated in both HP and PP groups when compared with HNP group. Earlier studies have reported increased IL-6 levels during the immediate postpartum period in healthy postpartum women (Groer et al., 2015; Ishikawa et al., 2004). Levels of IL–6 tend to increase during pregnancy and come down to the pre-pregnancy levels by 8–10 weeks postpartum (Gillespie et al., 2016). Therefore, the increased levels of IL-6 in both the HP and PP groups could be possibly suggestive of a normal postpartum physiological response. These findings probably suggest that pro-inflammatory cytokine IL-6 may not have an independent role in the pathogenesis of PP as it remains elevated in both the postpartum groups i.e., HP and PP. In our study, PP group as compared to HNP group showed significantly elevated levels of IL-8, while the levels in HP group were almost similar to that of the HNP group. This observation suggests a possible association of IL-8 with manifestation of PP. The literature about the role of IL-8 in PP is sparse. IL-8 has been found to be involved in the recruitment and activation of neutrophils, thereby playing an important role in acute inflammation (Harada et al., 1994). Evidence suggests that IL-8 levels have been significantly elevated in various psychiatric disorders including psychosis (Gariup et al., 2015). IL-8 has also been found to be associated with perinatal depression, first-episode acute psychosis and schizophrenia along with other proinflammatory cytokines (Di Nicola et al., 2013a; Osborne and Monk, 2013; Yang et al., 2002). Individuals with first episode acute psychosis having higher baseline levels of IL-8 responded well to antipsychotic medications (Di Nicola et al., 2013b; Mondelli et al., 2015). It is important to note that our patients were exposed to atypical antipsychotics, which are reported to have both pro- and anti-inflammatory effects in patients with psychosis (Sherer et al., 2017). Haring et al. studied the role of various antipsychotic medications on the cytokine levels in individuals with first-episode psychosis and demonstrated a significant reduction in the serum cytokine levels of IL-8 along with IL-1α IL-2, IL-4, IL-6 and IFN-γ (Haring et al., 2015). Hence, an elevation of IL-8 levels in PP group while being on antipsychotics as compared to HNP merits a further investigation into the relationship between atypical antipsychotics, postpartum psychosis, and IL-8 levels. A study by Bergink et al. reported elevated levels of IL-1β in the healthy postpartum control subjects as compared to healthy non-postpartum controls and also women in the first onset PP group had higher expression of MCP1 levels as compared to the other two groups i.e healthy postpartum and non-postpartum controls (Bergink et al., 2013). However, we did not find any such associations regarding the IL-1β levels and MCP1 levels in our study. Study of immune dysfunction has been an active area of interest in the pathophysiology of major psychiatric disorders. Peripheral cytokines level remains the main stay of assessment because of the ethical considerations involved in obtaining the cerebrospinal fluid or brain tissue. Peripheral cytokine levels may not exactly reflect the brain cytokine levels but can affect the production of cytokines in the brain. Further, these cytokines can act as mediators for synaptic plasticity at the tripartite synapse-astrocytes, pre-and post-synaptic neurons that serve as the relay system for immune-CNS interaction (Besedovsky and del Rey, 2011). A metanalysis of various cytokines in schizophrenia reports of elevated levels of IL-1β, IL- 6, IL-12, TGF-β, IFN- γ and sIL-2R (Soluble interleukin 2 receptor). IL- 6, TGF-β and IL-1β are considered as state markers for acute exacerbation of schizophrenia as they tend to normalize with antipsychotic treatment, whereas IL-12, IFN- γ and sIL-2R are considered more as trait marker (Miller et al., 2011). Similarly, a metanalysis of cytokine status in bipolar disorder reveals elevated levels of IL-1β, IL-4, IL- 6, IL-10 and TNF-α in mania (Modabbernia et al., 2013). Failure to detect similar associations among the cytokines that were examined in our study could suggest that first onset PP may have a different immune pathophysiology. However, this observation needs to be viewed with caution considering the fact that we did not include patients with schizophrenia and mania as controls in our study.