Antidepressants may mitigate the effects of prenatal maternal anxiety on infant auditory sensory gating

Abstract

Objective: Prenatal maternal anxiety has detrimental effects on the offspring's neurocognitive development, including impaired attentional function. Antidepressants are commonly used during pregnancy, yet their impact on offspring attention and their interaction with maternal anxiety has not been assessed. The authors used P50 auditory sensory gating, a putative marker of early attentional processes measurable in young infants, to assess the impact of maternal anxiety and antidepressant use.

Method: A total of 242 mother-infant dyads were classified relative to maternal history of anxiety and maternal prenatal antidepressant use. Infant P50 auditory sensory gating was recorded during active sleep at a mean age of 76 days (SD=38).

Results: In the absence of prenatal antidepressant exposure, infants whose mothers had a history of anxiety diagnoses had diminished P50 sensory gating. Prenatal antidepressant exposure mitigated the effect of anxiety. The effect of maternal anxiety was limited to amplitude of response to the second stimulus, while antidepressant exposure had an impact on the amplitude of response to both the first and second stimulus.

Conclusions: Maternal anxiety disorders are associated with less inhibition during infant sensory gating, a performance deficit mitigated by prenatal antidepressant exposure. This effect may be important in considering the risks and benefits of antidepressant use during pregnancy. Cholinergic mechanisms are hypothesized for both anxiety and antidepressant effects, although the cholinergic receptors involved are likely different for anxiety and antidepressant effects.

Figure 1

Individual examples of P50 sensory gating responses during active sleep. Clicks are presented 500 ms apart; the P50 response is noted by hashmarks. The positive P50 peak (hashmark above) was measured relative to the preceding negative trough (hashmark below). (a) An example of intact sensory gating in an infant at 44 weeks post last menstrual period (approximately 4-weeks of age). Note that the response test stimulus (on the right) is suppressed in comparison to the conditioning stimulus (on the left) for a P50 sensory gating ratio of 0.11. (b) An example of an infant also at 44 weeks post last menstrual period (approximately 4-weeks of age) with decreased sensory gating. This infant’s P50 response to the test stimulus (on the right) is similar to that for the conditioning stimulus (on the left), demonstrating lack of response suppression with a sensory gating ratio = 0.94.

Figure 2

Infant P50 ratios (mean ± SD) by group. Group membership is determined by the presence or absence of a maternal history of anxiety disorder and maternal prenatal antidepressant use. There is a significant effect of group membership (F=5.60, ndf=3, ddf=238, p=.001). Infants with a maternal history of an anxiety disorder but without prenatal exposure to antidepressants have P50 ratios significantly elevated compared to each of the other groups. The other groups do not significantly differ from each other. Differences that remain significant after Tukey-Kramer adjustment for multiple comparisons are denoted by an asterisk.

Figure 3

Infant P50 amplitudes in response to the first and second stimuli presented 500 ms apart. Values are means ± standard deviations. For amplitude of P50 response to the first stimulus, the effect of group is not significant (F=1.57, ndf=3, ddf=238, p=.197); however, when groups are collapsed across anxiety status, there is a significant effect of antidepressant exposure (t=2.06, df=240, p=.040). For amplitude of P50 response to the second stimulus, there is a significant effect of group (F=3.83, ndf=3, ddf=.010). For infants without prenatal antidepressant exposure, having a mother with a history of an anxiety disorder is associated with an elevated P50 amplitude in response to the second stimulus, an effect which is at least partially mitigated by prenatal exposure to antidepressants. Differences that remain significant after adjustment for multiple comparisons are denoted by an asterisk.