In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development.

Human epidemiological and animal-model studies suggest that separate exposure to stress or serotonin-selective reuptake inhibitor (SSRI) antidepressants during pregnancy increases risks for neurodevelopmental disorders in offspring. Yet, little is known about the combined effects of maternal stress and SSRIs with regard to brain development in utero. We found that the placenta is highly permeable to the commonly prescribed SSRI (±)-citalopram (CIT) in humans and mice, allowing rapid exposure of the fetal brain to this drug. We investigated the effects of maternal chronic unpredictable stress in mice with or without maternal oral administration of CIT from embryonic day (E)8 to E17. We assessed fetal brain development using magnetic resonance imaging and quantified changes in serotonergic, thalamocortical, and cortical development. In utero exposure to maternal stress did not affect overall fetal brain growth. However, serotonin tissue content in the fetal forebrain was increased in association with maternal stress; this increase was reversed by maternal CIT. In utero exposure to stress increased the numbers of deep-layer neurons in specific cortical regions, whereas CIT increased overall cell numbers without changing the proportions of layer-specific neurons to offset the effects of stress on deep-layer cortical development. These findings suggest that stress and SSRI exposure in utero differentially impact serotonin-dependent fetal neurodevelopment such that CIT reverses key effects of maternal gestational stress on offspring brain development.

A Conceptual Neurocognitive Affect-Related Model for the Promotion of Exercise Among Obese Adults.

PURPOSE OF REVIEW: Obesity remains a prominent societal threat and burden despite well-promoted prevention and treatment strategies, such as regular engagement in physical activity. Obese individuals, in particular, may be prone to inactivity as a result of a variety of displeasure-related parameters resulting from exercise, such as dyspnea, for instance. RECENT FINDINGS: This brief conceptual review discusses the integral roles of exercise-induced affective responses within a novel conceptual-based neurocognitive affect-related model. Specifically, this model includes three pathways: (1) pathway A proposes that neurocognition, and especially, executive function-based cognition, may play an influential role in fostering exercise-induced affective responses, (2) pathway B connects an individual's affective response from exercise to their future exercise behavior, and (3) pathway C suggests a cyclical, bi-directional relationship with executive function indirectly influencing future exercise behavior via affective responses to exercise, and exercise itself playing an important role in executive functioning. Future studies should empirically test this model, which may have utility for promoting exercise among the obese population.

Maternal Pharmacokinetics and Fetal Disposition of (±)-Citalopram during Mouse Pregnancy.

While selective-serotonin reuptake inhibitor (SSRI) antidepressants are commonly prescribed in the treatment of depression, their use during pregnancy leads to fetal drug exposures. According to recent reports, such exposures could affect fetal development and long-term offspring health. A central question is how pregnancy-induced physical and physiological changes in mothers, fetuses, and the placenta influence fetal SSRI exposures during gestation. In this study, we examined the effects of gestational stage on the maternal pharmacokinetics and fetal disposition of the SSRI (±)-citalopram (CIT) in a mouse model. We determined the maternal and fetal CIT serum concentration-time profiles following acute maternal administration on gestational days (GD)14 and GD18, as well as the fetal brain drug disposition. The results show that pregnancy affects the pharmacokinetics of CIT and that maternal drug clearance increases as gestation progresses. The data further show that CIT and its primary metabolite desmethylcitalopram (DCIT) readily cross the placenta into the fetal compartment, and fetal exposure to CIT exceeds that of the mother during gestation 2 h after maternal administration. Enzymatic activity assays revealed that fetal drug metabolic capacity develops in late gestation, resulting in elevated circulating and brain concentrations of DCIT at embryonic day (E)18. Fetal exposure to the SSRI CIT in murine pregnancy is therefore influenced by both maternal gestational stage and embryonic development, suggesting potential time-dependent effects on fetal brain development.

Development of a Conceptual Model for Smoking Cessation: Physical Activity, Neurocognition, and Executive Functioning.

PURPOSE: Considerable research has shown adverse neurobiological effects of chronic alcohol use, including long-term and potentially permanent changes in the structure and function of the brain; however, much less is known about the neurobiological consequences of chronic smoking, as it has largely been ignored until recently. In this article, we present a conceptual model proposing the effects of smoking on neurocognition and the role that physical activity may play in this relationship as well as its role in smoking cessation. METHODS: Pertinent published peer-reviewed articles deposited in PubMed delineating the pathways in the proposed model were reviewed. RESULTS: The proposed model, which is supported by emerging research, demonstrates a bidirectional relationship between smoking and executive functioning. In support of our conceptual model, physical activity may moderate this relationship and indirectly influence smoking behavior through physical activity-induced changes in executive functioning. CONCLUSIONS: Our model may have implications for aiding smoking cessation efforts through the promotion of physical activity as a mechanism for preventing smoking-induced deficits in neurocognition and executive function.

Physical activity and the brain: a review of this dynamic, bi-directional relationship.

The brain plays a major role in regulating physical activity behavior and exercise performance. Regular physical activity may also play a key role in the prevention and treatment of various neurological conditions, such as Parkinson's disease, Alzheimer's disease, depression, and cognitive function. This implies that not only does the brain (or the nervous system) regulate aspects of physical activity, but also that physical activity may potentially influence brain-related function and outcomes. This review details this bi-directional relationship and addresses its implications for improving physical activity, exercise performance, and brain-related function and outcomes.

Interactions of corticotropin-releasing factor, urocortin and citalopram in a primate model of stress-induced amenorrhea.

BACKGROUND/AIMS: We established a cynomolgus macaque model of stress-induced amenorrhea in which the application of combined metabolic and psychosocial stress suppressed ovulation in stress-sensitive (SS) individuals, but not in highly stress-resilient (HSR) individuals. We previously reported that SS monkeys have deficits in global serotonin release and serotonin-related gene expression in the raphe nucleus, and that administration of the selective serotonin reuptake inhibitor S-citalopram increased estrogen and progesterone production in SS monkeys. In this study, we questioned whether there was a difference in corticotropin-releasing factor (CRF) or urocortin (UCN) stress-related peptide systems in the midbrain raphe region when HSR and SS monkeys treated with placebo or S-citalopram are compared. METHODS: Monkeys characterized as HSR or SS were administered placebo or S-citalopram for 15 weeks. CRF fibers in the dorsal raphe were detected with an antibody against human CRF. UCN1 fibers were immunostained in an area rostral to the dorsal raphe. The fibers were quantified by stereology and analyzed by two-way ANOVA. UCN1 cell bodies were counted in the supraoculomotor area near the Edinger-Westphal nucleus. RESULTS: S-citalopram significantly decreased the CRF fiber density in SS animals, but not in HSR animals. SS monkeys had a significantly lower UCN1 fiber density compared to HSR monkeys, but S-citalopram treatment did not alter the UCN1 fiber density. SS animals treated with S-citalopram tended to have a higher number of UCN1-positive cell bodies than the other groups. CONCLUSION: S-citalopram decreased CRF fiber density and appears to increase the production of UCN1 in SS individuals, indicating the likelihood that serotonin is involved in regulating CRF and UCN1 in individuals who are sensitive to the effects of serotonin.