Exposure to Perinatal Infections and Bipolar Disorder: A Systematic Review

Abstract

Bipolar disorder (BD) is a debilitating psychiatric disorder and a growing global public health issue. Notwithstanding BD has been conceptualized as a neuroprogressive illness, there are some evidences to suggest a role for neurodevelopmental pathways in the patho-etiology of this disorder. Evidences on the associations between perinatal infections and risk for bipolar disorder have been inconsistent across studies. Here, we performed a systematic review of observational studies on the relationship between exposure to perinatal pathogens and bipolar disorder. A computerized literature search of the PubMed, Embase, and PsyINFO databases till January 31(st), 2015 was performed. Twenty-three studies ultimately met inclusion criteria. Studies investigated exposure to several pathogens namely Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Herpes simplex virus-1 (HSV-1), Herpes simplex virus-2 (HSV-2), Human herpesvirus 6 (HHV-6), Toxoplasma gondii, Influenza, and Varicella zoster virus (VZV). Overall, studies provided mixed evidences. Thus, contrary to schizophrenia, the role of perinatal infections as risk factors for BD remain inconclusive. Larger studies with a prospective design would be necessary to elucidate the role of previous exposure to infectious agents as a potential risk factor for BD.

Systematic assessment of environmental risk factors for bipolar disorder: an umbrella review of systematic reviews and meta‐analyses

“…Three articles reported prevalence rates of BD in medical conditions, namely endometriosis, fibromyalgia and multiple sclerosis . The remaining seven publications reported only systematic reviews . Figure presents a flow chart of study selection, and the reasons for exclusion are summarized in Supporting Information Table S1 (accompanying the online version of this article).…”

“…The median number of studies across these 37 systematic reviews was 3 (IQR 3−7). Of the seven publications, one included only case−control studies, two included mixed cross‐sectional and case−control studies, one included mixed prospective cohorts and nested case−control studies and the remaining three included mixed study designs (cross‐sectional, cohort and case−control) . The overall AMSTAR quality scores of the qualitative systematic reviews were low (median=2; IQR=1.5–2.5; Table S3, available online).…”

“…The studies reviewed across these qualitative systematic reviews are heterogeneous regarding classifications of exposures and do not provide directly comparable associations. For exposure to perinatal pathogens, the largest numbers of studies were found for cytomegalovirus (CMV) perinatal infection ( k =11), T. gondii perinatal infection ( k =9) and herpes simplex virus type 2 (HSV‐2) perinatal infection ( k =7) . For these three factors, the evidence was inconclusive or suggestive of no association with BD.…”

“…For these three factors, the evidence was inconclusive or suggestive of no association with BD. For CMV perinatal infection and T. gondii perinatal infection, only approximately half the studies suggested an association. The influenza virus perinatal infection was potentially associated with BD, as two out of three studies pointed to an association.…”

“…These data indicate that perinatal and early‐life insults may contribute to the pathophysiology of BD. Accordingly, previous systematic reviews indicate that perinatal infections (e.g., influenza and Toxoplasma gondii infection) may confer a higher risk of BD . In addition, exposure to childhood maltreatment is thought to increase the risk of BD, and also may have a detrimental impact on several BD‐related outcomes .…”