A large body of literature documents the adverse effects of maternal depression on the functioning and development of offspring. Although investigators have identified factors associated with risk for abnormal development and psychopathology in the children, little attention has been paid to the mechanisms explaining the transmission of risk from the mothers to the children. Moreover, no existing model both guides understanding of the various processes' interrelatedness and considers the role of development in explicating the manifestation of risk in the children. This article proposes a developmentally sensitive, integrative model for understanding children's risk in relation to maternal depression. Four mechanisms through which risk might be transmitted are evaluated: (a) heritability of depression; (b) innate dysfunctional neuroregulatory mechanisms; (c) exposure to negative maternal cognitions, behaviors, and affect; and (d) the stressful context of the children's lives. Three factors that might moderate this risk are considered: (a) the father's health and involvement with the child, (b) the course and timing of the mother's depression, and (c) characteristics of the child. Relevant issues are discussed, and promising directions for future research are suggested.

Risk for psychopathology in the children of depressed mothers: a developmental model for understanding mechanisms of transmission.

/pdf/practice-guideline-for-the-treatment-of-patients-with-major-ofberaz3o1.pdf

PRACTICE GUIDELINE FOR THE Treatment of Patients With Major Depressive Disorder

ACOG practice bulletin: Clinical management guidelines for obstetrician-gynecologists

Reduced serotonin transporter (5-HTT) expression is associated with abnormal affective and anxiety-like symptoms in humans and rodents, but the mechanism of this effect is unknown. Transient inhibition of 5-HTT during early development with fluoxetine, a commonly used serotonin selective reuptake inhibitor, produced abnormal emotional behaviors in adult mice. This effect mimicked the behavioral phenotype of mice genetically deficient in 5-HTT expression. These findings indicate a critical role of serotonin in the maturation of brain systems that modulate emotional function in the adult and suggest a developmental mechanism to explain how low-expressing 5-HTT promoter alleles increase vulnerability to psychiatric disorders.

https://science.sciencemag.org/content/sci/306/5697/879.full.pdf

Early-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice

The sodium-dependent, high affinity serotonin [5-hydroxytryptamine (5-HT)] transporter (5-HTT) provides the primary mechanism for inactivation of 5-HT after its release into the synaptic cleft. To further evaluate the function of the 5-HTT, the murine gene was disrupted by homologous recombination. Despite evidence that excess extracellular 5-HT during embryonic development, including that produced by drugs that inhibit the 5-HTT, may lead to severe craniofacial and cardiac malformations, no obvious developmental phenotype was observed in the 5-HTT−/− mice. High affinity [3H]5-HT uptake was completely absent in 5-HTT−/− mice, confirming a physiologically effective knockout of the 5-HTT gene. 5-HTT binding sites labeled with [125I]3β-(4′-iodophenyl)tropan-2β-carboxylic acid methyl ester were reduced in a gene dose-dependent manner, with no demonstrable binding in 5-HTT−/− mutants. In adult 5-HTT−/− mice, marked reductions (60–80%) in 5-HT concentrations were measured in several brain regions. While (+)-amphetamine-induced hyperactivity did not differ across genotypes, the locomotor enhancing effects of (+)-3,4-methylenedioxymethamphetamine, a substituted amphetamine that releases 5-HT via a transporter-dependent mechanism, was completely absent in 5-HTT−/− mutants. Together, these data suggest that the presence of a functional 5-HTT is essential for brain 5-HT homeostasis and for 3,4-methylenedioxymethamphetamine-induced hyperactivity.

Altered Brain Serotonin Homeostasis and Locomotor Insensitivity to 3,4-Methylenedioxymethamphetamine (“Ecstasy”) in Serotonin Transporter-Deficient Mice

Background Many women of reproductive age have depression, necessitating therapy with either a tricyclic antidepressant drug or a drug, such as fluoxetine, that inhibits the reuptake of serotonin. Whether these drugs affect fetal neurodevelopment is not known. Methods We studied the children of 80 mothers who had received a tricyclic antidepressant drug during pregnancy, 55 children whose mothers had received fluoxetine during pregnancy, and 84 children whose mothers had not been exposed during pregnancy to any agent known to affect the fetus adversely. The children's global IQ and language development were assessed between 16 and 86 months of postnatal age by age-appropriate Bayley Scales of Infant Development or the McCarthy Scales of Children's Abilities (for IQ) and the Reynell Developmental Language Scales. Results The mean (±SD) global IQ scores were 118±17 in the children of mothers who received a tricyclic antidepressant drug, 117±17 in those whose mothers received fluoxetine, and 115±14 in those ...

H. A. Gardner

Papers

Neurodevelopment of Children Exposed in Utero to Antidepressant Drugs