Variation in adult anxiety and serotonin transmission following early exposure to different antidepressants

Create: 12/26/2014 - 07:00

Many women suffer from depression and anxiety disorders during pregnancy- about 15% in the United States for example- and a proportion of these will be prescribed antidepressants, leading to prenatal exposure to these drugs for their infants. In the United States, this equates to approximately 5% of all infants being exposed prenatally to antidepressants. However, the long-term effects on these children are largely unknown. A new study published in the journal Neuropsychopharmacology has shown that rodents exposed to two different antidepressants, escitalopram (ESC; Lexapro®) or fluoxetine (Prozac®) exhibited different anxiety-related behaviour and serotonin neurotransmission in adulthood. This has implications for prescribing safe antidepressants for pregnant women.

Prozac and Lexapro are both serotonin-selective reuptake inhibiting antidepressants (SSRIs) and were thought to act in the same way on the serotonin transport system by blocking the serotonin transporter (SERT) and removing this neurotransmitter from the signalling space between neurons. Genetic serotonin transporters reduction is thought to be a risk factor for development of anxiety and mood disorders.

In the current study, the research team used a mouse model that mimics human third trimester medication exposure. The results indicated that in the mice exposed to escitalopram, there was a lifelong reduction in anxiety-related behaviour, associated with hypofunction of the adult serotonin system in the hippocampal area of the brain. This was in contrast to the fluoxetine-treated mice, who exhibited behavioural changes somewhat similar to SERT deficiency, although not accompanied by changes in hippocampal serotonin transmission.

Senior study author Prof Anne M. Andrews, of the Semel Institute for Neuroscience & Human Behavior and California NanoSystems Institute said: "This was quite surprising, since these medications belong to the same drug class and are believed to work by the same mechanism. The implications of these findings are that with additional investigation, it may be possible to identify specific antidepressants that are safer for pregnant women…It's important to recognize that major depressive disorders and anxiety disorders are serious medical conditions that often require therapeutic intervention. Prescribing the safest medication for mother and child is paramount…It might be possible that when mothers are treated for depression or anxiety during pregnancy that certain SSRIs may promote resilience to developing these disorders in children later in life. However, it will take much more research for us to understand whether this is true and whether certain SSRIs may be better at promoting these effects."

The research team now plan to investigate the effects of early exposure to antidepressants on the architectures of serotonin neurons. The current study results suggest that early exposure to escitalopram may alter the way serotonin neurons innervate brain regions involved in mood and anxiety behaviour. Other SSRIs such as Paxil and Zoloft will also be included in future studies.

Science news reference:

Perinatal vs. Genetic Programming of Serotonin States Associated with Anxiety. Altieri SC, Yang H, O'Brien HJ, Redwine HM, Senturk D, Hensler JG, Andrews AM. Neuropsychopharmacology (19 December 2014) | doi:10.1038/npp.2014.331

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