The decay of mRNA plays a vital role in modulating mRNA abundance, which, in turn, influences cellular and organismal processes. In plants and metazoans, three distinct pathways carry out the decay of most cytoplasmic mRNAs: The mRNA decapping complex, which requires the scaffold protein VARICOSE (VCS), removes a protective 5' cap, allowing for 5' to 3' decay via EXORIBONUCLEASE4 (XRN4, XRN1 in metazoans and yeast), and both the exosome and SUPPRESSOR OF VCS (SOV)/DIS3L2 degrade RNAs in the 3' to 5' direction. However, the unique biological contributions of these three pathways, and whether they degrade specialized sets of transcripts, are unknown. In , the participation of SOV in RNA homeostasis is also unclear, because mutants have a normal phenotype. We carried out mRNA decay analyses in wild-type, ,, and seedlings, and used a mathematical modeling approach to determine decay rates and quantify gene-specific contributions of VCS and SOV to decay. This analysis revealed that VCS (decapping) contributes to decay of 68% of the transcriptome, and, while it initiates degradation of mRNAs with a wide range of decay rates, it especially contributes to decay of short-lived RNAs. Only a few RNAs were clear SOV substrates in that they decayed more slowly in mutants. However, 4,506 RNAs showed VCS-dependent feedback in that modulated decay rates, and, by inference, transcription, to maintain RNA abundances, suggesting that these RNAs might also be SOV substrates. This feedback was shown to be independent of siRNA activity.

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.

Background Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments and whether observed memory effects are specific to a particular modality, that is, verbal versus visual/spatial domains. Methods In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol-exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic Group, n=47); Exposed individuals without such effects (n=74). Contrast groups included: Controls (n=59) matched for ethnicity, socioeconomic status and hospital of birth; Special Education contrast group (n=54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval and learning over trials as indexed by slope. Results Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured but they did not differ from those in the Special Education contrast group. The non-dysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance. Conclusion These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance and that these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.

Context Despite the expanding clinical utility of antipsychotics beyond psychotic disorders to include depressive, bipolar, and anxiety disorders, reproductive safety data regarding the neurodevelopmental sequelae of fetal antipsychotic exposure are scarce. Objective To examine whether intrauterine antipsychotic exposure is associated with deficits in neuromotor performance and habituation in 6-month-old infants. Design, Setting, and Participants A prospective controlled study was conducted from December 1999 through June 2008 at the Infant Development Laboratory of the Emory Psychological Center examining maternal-infant dyads (N=309) at 6 months postpartum with pregnancy exposure to antipsychotics (n=22), antidepressants (n = 202), or no psychotropic agents (n = 85). Examiners masked to maternal-infant exposure status administered a standardized neuromotor examination (Infant Neurological International Battery [INFANIB]) that tests posture, tone, reflexes, and motor skills and a visual habituation paradigm using a neutral female face. Main Outcome Measures The INFANIB composite score; number of trials required to achieve a 50% decrease in infant fixation during a visual habituation task; and mean time looking at the stimulus across 10 trials. Results Infants prenatally exposed to antipsychotics (mean=64.71) showed significantly lower INFANIB scores than those with antidepressant (mean=68.57) or no psychotropic (mean=71.19) exposure, after controlling for significant covariates (F2,281=4.51; P =.01; partial η2=0.033). The INFANIB scores were also significantly associated with maternal psychiatric history, including depression, psychosis, and overall severity/chronicity (P’s<.05) and maternal depression during pregnancy was associated with less efficient habituation (r245=0.16; P <.02). There were no significant differences regarding habituation between medication exposure groups. Conclusions Among 6-month-old infants, a history of intrauterine antipsychotic exposure, compared with antidepressant or no psychotropic exposure, was associated with significantly lower scores on a standard test of neuromotor performance, highlighting the need for further scrutiny of the reproductive safety and neurodevelopmental sequelae of fetal antipsychotic exposure. Disentangling medication effects from maternal illness effects, which also contributed, remains a critical challenge.

A history of childhood trauma is associated with increased risk for psychopathology and interpersonal difficulties in adulthood and, for those who have children, impairments in parenting and increased risk of negative outcomes in offspring. Physiological and behavioral mechanisms are poorly understood. In the current study, maternal history of childhood trauma was hypothesized to predict differences in maternal affect and HPA axis functioning. Mother-infant dyads (N = 255) were assessed at 6 months postpartum. Mothers were videotaped during a 3-min naturalistic interaction, and their behavior was coded for positive, neutral, and negative affect. Maternal salivary cortisol was measured six times across the study visit, which also included an infant stressor paradigm. Results showed that childhood trauma history predicted increased neutral affect and decreased mean cortisol in the mothers and that cortisol mediated the association between trauma history and maternal affect. Maternal depression was not associated with affective measures or cortisol. Results suggest that early childhood trauma may disrupt the development of the HPA axis, which in turn impairs affective expression during mother-infant interactions in postpartum women. Interventions aimed at treating psychiatric illness in postpartum women may benefit from specific components to assess and treat trauma-related symptoms and prevent secondary effects on parenting.