SSRI exposure in utero may change brain structure and connectivity

Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) was associated with fetal brain development in brain regions important in emotional processing, results of an imaging study show.

Compared to controls, SSRI-exposed infants had significant gray matter volume expansion and increased white matter structural connectivity in the amygdala and insula, according to results published in JAMA Pediatrics.

“Our findings suggest a potential association between prenatal SSRI exposure, likely via aberrant serotonin signaling, and the development of the amygdala-insula circuit in the fetal brain,” wrote Claudia Lugo-Candelas, PhD, of Columbia University Medical Center, New York, and her coauthors.

An increasing number of pregnant women are taking SSRIs, in part due to increased awareness of the negative effects of untreated prenatal maternal depression (PMD), the investigators said in their report.

“Because untreated PMD poses risks to both the infant and mother, the decision to initiate, continue, or suspend SSRI treatment remains a clinical dilemma,” they wrote.

Animal studies suggest atypical serotonergic signaling from prenatal SSRI exposure could change fetal brain development and affect function later in life, they explained.

Studies in humans have produced mixed results, but in a recent national registry study including more than 15,000 individuals exposed to SSRIs prenatally, exposure was linked to increased rates of depression.

To evaluate the impact of prenatal SSRI exposure on brain development, Dr. Lugo-Candelas and colleagues used structural and diffusion magnetic resonance imaging (MRI) to evaluate the brains of 98 infants.

They included 16 infants with in utero exposure to SSRIs, 21 born to mothers with untreated maternal depression, and 61 healthy control subjects, all evaluated between 2011 and 2016.

Infants exposed to SSRIs in utero had significant (P less than .05) gray matter volume expansion versus controls in both the right amygdala (Cohen’s d, 0.65; 95 %CI, 0.06-1.23) and the right insula (Cohen’s d = 0.86; 95% CI, 0.26-1.14).

The SSRI-exposed infants also had a significant (P less than .05) increase in connectivity between the right amygdala and the right insula versus controls (Cohen’s d, 0.99; 95% CI, 0.40-1.57).

Whether these neurodevelopmental changes translate into long-term behavioral or psychological outcomes should be evaluated in subsequent studies, Dr. Lugo-Candelas and colleagues said.

Abnormalities in amygdala-insula circuitry may lead to anxiety or depression, they wrote.

“The structurally primed circuit in the infant brains could lead to maladaptive fear processing in their later life, such as generalization of conditioned fear or negative attention bias,” they added.

Dr. Lugo-Candelas reported no conflicts of interest related to the study. One study coauthor reported research support from Shire Pharmaceuticals and Aevi Genomics.

SOURCE: Lugo-Candelas C, et al. JAMA Pediatr. 2018 Apr 9. doi: 10.1001/jamapediatrics.2017.5227.

Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) was associated with fetal brain development in brain regions important in emotional processing, results of an imaging study show.

Compared to controls, SSRI-exposed infants had significant gray matter volume expansion and increased white matter structural connectivity in the amygdala and insula, according to results published in JAMA Pediatrics.

“Our findings suggest a potential association between prenatal SSRI exposure, likely via aberrant serotonin signaling, and the development of the amygdala-insula circuit in the fetal brain,” wrote Claudia Lugo-Candelas, PhD, of Columbia University Medical Center, New York, and her coauthors.

An increasing number of pregnant women are taking SSRIs, in part due to increased awareness of the negative effects of untreated prenatal maternal depression (PMD), the investigators said in their report.

“Because untreated PMD poses risks to both the infant and mother, the decision to initiate, continue, or suspend SSRI treatment remains a clinical dilemma,” they wrote.

Animal studies suggest atypical serotonergic signaling from prenatal SSRI exposure could change fetal brain development and affect function later in life, they explained.

Studies in humans have produced mixed results, but in a recent national registry study including more than 15,000 individuals exposed to SSRIs prenatally, exposure was linked to increased rates of depression.

To evaluate the impact of prenatal SSRI exposure on brain development, Dr. Lugo-Candelas and colleagues used structural and diffusion magnetic resonance imaging (MRI) to evaluate the brains of 98 infants.

They included 16 infants with in utero exposure to SSRIs, 21 born to mothers with untreated maternal depression, and 61 healthy control subjects, all evaluated between 2011 and 2016.

Infants exposed to SSRIs in utero had significant (P less than .05) gray matter volume expansion versus controls in both the right amygdala (Cohen’s d, 0.65; 95 %CI, 0.06-1.23) and the right insula (Cohen’s d = 0.86; 95% CI, 0.26-1.14).

The SSRI-exposed infants also had a significant (P less than .05) increase in connectivity between the right amygdala and the right insula versus controls (Cohen’s d, 0.99; 95% CI, 0.40-1.57).

Whether these neurodevelopmental changes translate into long-term behavioral or psychological outcomes should be evaluated in subsequent studies, Dr. Lugo-Candelas and colleagues said.

Abnormalities in amygdala-insula circuitry may lead to anxiety or depression, they wrote.

“The structurally primed circuit in the infant brains could lead to maladaptive fear processing in their later life, such as generalization of conditioned fear or negative attention bias,” they added.

Dr. Lugo-Candelas reported no conflicts of interest related to the study. One study coauthor reported research support from Shire Pharmaceuticals and Aevi Genomics.

SOURCE: Lugo-Candelas C, et al. JAMA Pediatr. 2018 Apr 9. doi: 10.1001/jamapediatrics.2017.5227.

Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) was associated with fetal brain development in brain regions important in emotional processing, results of an imaging study show.

Compared to controls, SSRI-exposed infants had significant gray matter volume expansion and increased white matter structural connectivity in the amygdala and insula, according to results published in JAMA Pediatrics.

“Our findings suggest a potential association between prenatal SSRI exposure, likely via aberrant serotonin signaling, and the development of the amygdala-insula circuit in the fetal brain,” wrote Claudia Lugo-Candelas, PhD, of Columbia University Medical Center, New York, and her coauthors.

An increasing number of pregnant women are taking SSRIs, in part due to increased awareness of the negative effects of untreated prenatal maternal depression (PMD), the investigators said in their report.

“Because untreated PMD poses risks to both the infant and mother, the decision to initiate, continue, or suspend SSRI treatment remains a clinical dilemma,” they wrote.

Animal studies suggest atypical serotonergic signaling from prenatal SSRI exposure could change fetal brain development and affect function later in life, they explained.

Studies in humans have produced mixed results, but in a recent national registry study including more than 15,000 individuals exposed to SSRIs prenatally, exposure was linked to increased rates of depression.

To evaluate the impact of prenatal SSRI exposure on brain development, Dr. Lugo-Candelas and colleagues used structural and diffusion magnetic resonance imaging (MRI) to evaluate the brains of 98 infants.

They included 16 infants with in utero exposure to SSRIs, 21 born to mothers with untreated maternal depression, and 61 healthy control subjects, all evaluated between 2011 and 2016.

Infants exposed to SSRIs in utero had significant (P less than .05) gray matter volume expansion versus controls in both the right amygdala (Cohen’s d, 0.65; 95 %CI, 0.06-1.23) and the right insula (Cohen’s d = 0.86; 95% CI, 0.26-1.14).

The SSRI-exposed infants also had a significant (P less than .05) increase in connectivity between the right amygdala and the right insula versus controls (Cohen’s d, 0.99; 95% CI, 0.40-1.57).

Whether these neurodevelopmental changes translate into long-term behavioral or psychological outcomes should be evaluated in subsequent studies, Dr. Lugo-Candelas and colleagues said.

Abnormalities in amygdala-insula circuitry may lead to anxiety or depression, they wrote.

“The structurally primed circuit in the infant brains could lead to maladaptive fear processing in their later life, such as generalization of conditioned fear or negative attention bias,” they added.

Dr. Lugo-Candelas reported no conflicts of interest related to the study. One study coauthor reported research support from Shire Pharmaceuticals and Aevi Genomics.

SOURCE: Lugo-Candelas C, et al. JAMA Pediatr. 2018 Apr 9. doi: 10.1001/jamapediatrics.2017.5227.