Neurogenic Plasticity in a Serotonin Transporter Knockout Model: Effects of Maternal and Offspring Genotype

<p>Major depressive disorder (MDD) is debilitating mental disorder that is increasing in prevalence. Many theories have tried to explain the aetiology of depression including the classic monoamine deficiency hypothesis and the newer neurogenic hypothesis. The finding that selective serotonin transporter inhibitors (SSRIs) work by increasing extracellular serotonin levels in the brain and have antidepressant effects has formed the basis of the most widely accepted theory of depression, the monoamine hypothesis. However, a genetic reduction in human and animal serotonin reuptake transporters, which also increases extracellular serotonin, is associated with depressive symptomology. This paradox is not explained by the monoamine hypothesis. The key difference between these two scenarios is that genetically induced increases in serotonin occur from development onward, while SSRIs increase serotonin only in adulthood. Furthermore, SSRIs typically take several weeks to confer a therapeutic effect. This finding has led to the hypothesis that, rather than acute monoamine-increasing effects, it is the downstream effects of such increases on neurogenesis and neural plasticity which confer antidepressant effects. To further elucidate the neurobiology of depression, this study sought to examine the effects of genetically increasing serotonin on early postnatal neurogenesis in a serotonin knockout rat model using BrdU immunohistochemistry. We examined both the offspring and maternal genotype effects. We found that SERT-/- offspring had the highest levels of neurogenesis compared with SERT+/- and SERT+/+ at postnatal day 7. In addition we found a maternal genotype effect with SERT+/+ offspring born and reared by SERT+/- mothers having lower neurogenesis compared to SERT+/+ offspring from SERT+/+ mothers. The potential effects of maternal caregiving, neuroplasticity in altered mood and stress responses and the role of 5-HT receptors are discussed.</p>

Neurogenic Plasticity in a Serotonin Transporter Knockout Model: Effects of Maternal and Offspring Genotype

<p>Major depressive disorder (MDD) is debilitating mental disorder that is increasing in prevalence. Many theories have tried to explain the aetiology of depression including the classic monoamine deficiency hypothesis and the newer neurogenic hypothesis. The finding that selective serotonin transporter inhibitors (SSRIs) work by increasing extracellular serotonin levels in the brain and have antidepressant effects has formed the basis of the most widely accepted theory of depression, the monoamine hypothesis. However, a genetic reduction in human and animal serotonin reuptake transporters, which also increases extracellular serotonin, is associated with depressive symptomology. This paradox is not explained by the monoamine hypothesis. The key difference between these two scenarios is that genetically induced increases in serotonin occur from development onward, while SSRIs increase serotonin only in adulthood. Furthermore, SSRIs typically take several weeks to confer a therapeutic effect. This finding has led to the hypothesis that, rather than acute monoamine-increasing effects, it is the downstream effects of such increases on neurogenesis and neural plasticity which confer antidepressant effects. To further elucidate the neurobiology of depression, this study sought to examine the effects of genetically increasing serotonin on early postnatal neurogenesis in a serotonin knockout rat model using BrdU immunohistochemistry. We examined both the offspring and maternal genotype effects. We found that SERT-/- offspring had the highest levels of neurogenesis compared with SERT+/- and SERT+/+ at postnatal day 7. In addition we found a maternal genotype effect with SERT+/+ offspring born and reared by SERT+/- mothers having lower neurogenesis compared to SERT+/+ offspring from SERT+/+ mothers. The potential effects of maternal caregiving, neuroplasticity in altered mood and stress responses and the role of 5-HT receptors are discussed.</p>

Maternal caregiving ameliorates the consequences of prenatal maternal psychological distress on child development

Children exposed to prenatal maternal psychological distress are at elevated risk for a range of adverse outcomes; however, it remains poorly understood whether postnatal influences can ameliorate impairments related to prenatal distress. The current study evaluated if sensitivematernal care during the first postnatal year could mitigate child cognitive and emotional impairments associated with prenatal psychological distress. Prenatal maternal psychological distress was assessed via self-reports of anxiety, depression, and perceived stress for 136 mothers at five prenatal and four postpartum time points. Quality of maternal care (sensitivity to nondistress, positive regard, and intrusiveness reverse-scored) were assessed during a mother–child play interaction at 6 and 12 months. Child cognitive function and negative emotionality were assessed at 2 years, using The Bayley Scales and the Early Childhood Behavior Questionnaire. Elevated prenatal distress was associated with poorer child cognitive function and elevated negative emotionality. Children exposed to elevated prenatal maternal distress did not, however, display these outcomes if they received high-quality caregiving. Specifically, maternal care moderated the relation between prenatal psychological distress and child cognitive function and negative emotionality. This association remained after consideration of postnatal maternal psychological distress and relevant covariates. Sensitive maternal care was associated with altered offspring developmental trajectories, supporting child resilience following prenatal distress exposure.

Maternal Alexithymic Traits Are Related to Lower Maternal Sensitivity and Higher Hostility in Maternal Caregiving Behavior—The FinnBrain Birth Cohort Study

Background: The quality of parental caregiving behavior with their child plays a key role in optimal mother–infant interaction and in supporting child adaptive development. Sensitive caregiving behavior, in turn, requires the ability to identify and understand emotions. Maternal alexithymia, with difficulties in identifying and describing feelings or emotions, as well as a concrete way of thinking, could potentially complicate the quality of caregiving. In this study, we aim to explore the possible association between maternal alexithymic traits and the quality of maternal caregiving behavior.Methods: The study sample consisted of 158 mother–infant dyads within the FinnBrain Birth Cohort Study population with an available report of maternal alexithymic traits at 6 months postpartum and observational data on maternal caregiving behavior at 8 months postpartum. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20) including three alexithymia dimensions—Difficulty Identifying Feelings, Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Maternal caregiving behavior was assessed using the Emotional Availability Scale and in this study, all four parent dimensions (Sensitivity, Structuring, Non-intrusiveness and Non-hostility) were included. Maternal depressive and anxiety symptoms at 6 months postpartum were controlled for as potential confounders. In addition, background factors of mother's age and gestational weeks at the time of child birth, maternal educational level, monthly income and parity, as well as relationship status and the gender of the baby were assessed.Results: Maternal TAS-20 total score correlated negatively with Sensitivity (r = −0.169, p = 0.034) and with non-intrusiveness (r = −0.182, p = 0.022). In addition, maternal DDF correlated negatively with Sensitivity (r = −0.168, p = 0.035) and EOT with Non-hostility (r = −0.159, p = 0.047). Furthermore, in regression analyses with controlling for the associated background factors, maternal total score of alexithymic traits (p = 0.034, η2p = 0.029) and higher DDF (p = 0.044, η2p = 0.026) remained significantly associated with lower Sensitivity and higher EOT remained significantly associated with lower Non-hostility (p = 0.030, η2p = 0.030).Conclusions: In this explorative study we found preliminary evidence for the hypothesis that higher maternal alexithymic traits associate with lower maternal sensitivity and more hostile maternal caregiving behavior. Further studies are needed to explore these hypotheses and to investigate their possible implications for child development.