Although the onset and manifestation of neuropsychiatric disorders such as autism spectrum disorder, schizophrenia, attention deficit/hyperactivity disorder and bipolar disorder are highly variable in patients, common characteristics that underlie many of these conditions suggest that they share common causes. Epidemiological and clinical studies have identified links between these disorders and a family history of immune conditions. Although heritable genetic traits likely influence these phenomena, current data suggests that external, environmental factors likely contribute even more strongly to their onset and severity. Most notably, mothers who have experienced increased immune activity during pregnancy, such as from infection or inflammatory reactions, are more likely to have a child with one of these neuropsychiatric disorders. Additionally, preclinical research suggests that pathogenic infections during gestation do not directly induce psychiatric disorder in the offspring; instead, it is the immune response, including inflammation, triggered by the infection that contributes to the phenomena.
In a recent study in Translational Psychiatry, a team led by Dr. Jared Schwartzer of Mount Holyoke College and Dr. Paul Ashwood of the University of California at Davis demonstrate that the incidences of developmental behavioral disorders are increased in mice born from dams with induced asthma. This mouse model demonstrating the link between immune responses and neurodevelopmental disorders may reveal targets for therapy and prevention, as well as novel interactions between immune signaling and neurological development for future research.
To study the effect of immune system perturbation in pregnant mothers on the development of their offspring, the researchers sensitized virgin C57BL/6J (000664) females with two intraperitoneal injections of ovalbumin (OVA). One week after the last injection, the females were mated overnight with male C57BL/6J mice. Pregnant mice were identified by presence of a seminal plug and then assigned to an allergic asthma or control group: the former received an aerosolized OVA solution, the latter received aerosolized vehicle alone. The pregnant females received three treatments during the gestational period to induce airway inflammation. No significant differences were observed in either the pregnancies or deliveries in either group, but pups born from asthmatic mothers were longer and weighed more than pups from the control mothers. Although the weight difference did not persist beyond two weeks of age, mice from asthmatic dams remained longer in length into adulthood.
The effect of maternal OVA-induced airway inflammation on social and cognitive behaviors was measured through a number of tasks, including: a three-chambered social approach, a social dominance tube, marble burying, grooming, locomotor activity, novel-object recognition, and an elevated plus maze. Notably, offspring from OVA-exposed dams were less social and demonstrated increased marble-burying behavior, both of which are analogous to the social and repetitive behavior patterns observed in a spectrum of neurodevelopmental disorders. Western blot analysis of serotonin transporter (SERT) protein expression from the cortex of mice from asthmatic dams demonstrated an increase in SERT compared to those from control dams. Because dysregulated serotonin signaling is associated with a number of cognitive and behavioral conditions (selective serotonin uptake inhibitors are commonly prescribed to many patients with these disorders), this data forges a novel link between exogenous inflammatory signaling and neurological development.
The mechanisms of this interaction are not yet known, but the potential impact upon human health is significant. Allergy and asthma rates are increasing in many populations, probably due to the effects of air pollutants and other stimuli. Studies such as the one reported here will be valuable in designing prevention or treatment regimens for pregnant mothers or their children affected by neurological disorders.