Schizophrenia is a chronic and pervasive neurodevelopmental disorder that devastates the lives of nearly 1% of the population. The disorder is most commonly recognized by the manifestation of hallucinations, delusions, and bizarre or disorganized behavior. These psychotic symptoms are only one facet of this complex illness. Individuals with schizophrenia also experience disabling cognitive, affective, and social impairments. Dysfunction of brain dopamine systems, and the mesocorticolimbic system in particular, is suspected to underlie these impairments. Despite recognition of the illness throughout history, there are currently no effective interventions ameliorating the full spectrum of the illness, and the origins of schizophrenia remain unclear.
Although genetic factors contribute substantially to the etiology of schizophrenia, it is clear that environmental factors have a significant pathophysiological role. Epidemiologic evidence suggests that the prenatal period represents a critical window of vulnerability to environmental insult. Multiple prenatal exposures are associated with elevated schizophrenia risk in later life, including maternal infection, psychosocial stress, malnutrition, and obstetric complications. It is theorized that a mechanism common to these diverse insults may disrupt fetal development, therefore leading to psychiatric illness. One such common factor of these prenatal events is activation of the maternal inflammatory response during pregnancy.
The objective of the following work was to determine the consequences of maternal immune stimulation during pregnancy on behaviors mediated by the mesocorticolimbic dopamine system in exposed progeny. Mesocorticolimbic dopamine neurotransmission is thought to underlie psychosis symptoms, as well as their exacerbation by psychomimetic agents and psychosocial stress. Thus, these studies test the overarching hypothesis that prenatal immune activation would enhance the behavioral response to psychomimetic drugs and stressful stimuli. The following work provides data evidencing complex effects on mesocorticolimbic sensitivity to these stimuli that vary depending on the specific immunostimulatory agent and environmental exposures in offspring. These data support a relationship between the maternal inflammatory response and fetal maldevelopment, and implicate intermediary mechanisms downstream of bacterial-like immune activation.