Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, post-concussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/ treatment interventions. Progress in overcoming these limitations has been challenging, because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large scale (n = 5,000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for one year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

An early first pregnancy is known to protect against subsequent breast cancer. We speculated that this effect may be mediated by a long-term depression of prolactin secretion after pregnancy. We therefore measured basal and post-stimulation serum levels of prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in two groups--15 women 18 to 23 years of age and 9 women 29 to 40--before and after a first full-term pregnancy, and in 40 appropriate nulliparous controls. We observed no significant change in basal levels of serum LH or FSH or in the levels stimulated by gonadotropin-releasing hormone in any group. A significant decrease was seen, however, in basal and perphenazine-stimulated levels of prolactin after pregnancy in both the younger and older first-pregnancy groups but not in the controls. In a separate cross-sectional study, we compared basal serum prolactin levels in 29 parous and 19 nulliparous women of similar age. The serum prolactin levels were significantly lower in the parous group but were not related to the number of pregnancies (one to three) or the time elapsed (12 to 150 months) since the last delivery. We conclude that a first pregnancy leads to a long-term decrease in serum prolactin secretion, lasting at least 12 to 13 years.

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We compared daily urinary concentrations of oestrogen and progesterone metabolites in paired menstrual cycles (conception and non-conception) from 32 women. Volunteers with no known fertility problems were enrolled in the study at the time they began trying to become pregnant. They collected first-morning urine specimens and kept daily records of menstrual bleeding and sexual intercourse for 6 months or until they became clinically pregnant. Intercourse in non-conception cycles was close to the time of ovulation so that failure to conceive was caused by factors other than poorly timed intercourse. Compared with non-conception cycles, conception cycles had a steeper early luteal rise in progesterone and higher mid-luteal oestrogen and progesterone concentrations. These hormonal characteristics may be markers of better quality cycles, but because all these differences were in the luteal phase, we cannot rule out the possibility that the preimplantation embryo had stimulated early increases in steroid production. We propose an analysis strategy that could help support or refute the importance of preimplantation embryonic signalling, but our small sample size limits our own conclusions about this mechanism.

An early (but not a late) first pregnancy is known to be protective for breast cancer. This effect might be mediated through a long term change in the hormonal environment caused by the early first pregnancy. To investigate the possibility of such a change we carried out a prospective longitudinal study of serum and urinary estrogens and serum androgens in four groups of women, namely early (age, 18-23 yr) first pregnancy (n = 15), early control (n = 20), late (age, 29-40 yr) first pregnancy (n = 9), and late control (n = 20). The pregnancy groups were studied before (initial visit) and 7-19 months after a first pregnancy (return visit). The control groups were similarly studied, but without an intervening pregnancy. The following were measured: serum estrone (E1), 17 beta-estradiol (E2), estriol (E3), and E1 sulfate; urinary total E1, E2, E3, and glucosiduronates of these three estrogens; and serum testosterone, dehydroepiandrosterone sulfate (DHAS), and dehydroepiandrosterone (DHA). There was no significant change between the initial and return visits in serum E1, E2, E1 sulfate, or any of the urinary estrogens in either pregnancy group or in the corresponding control groups. There was, however, a significant increase in serum E3 between initial and return visits for both pregnancy groups compared with the control values. There was no significant change in serum testosterone. There was a marked significant decrease in both serum DHAS and DHA between initial and return visits in both pregnancy groups compared with the corresponding control group values. There was also a significant increase in the serum E3 to DHA ratio in both pregnancy groups. A cross-sectional study (measuring serum DHAS and DHA only) was then carried out in a series of parous and nulliparous women. The serum DHAS and DHA levels were markedly and significantly lower in parous than in nulliparous women, as expected. There was no significant relationship between serum DHAS or DHA levels and months elapsed (up to 150) since last delivery, indicating that the changes last at least for this period of time. There was no significant relationship between serum DHAS or DHA levels and parity (one to three previous pregnancies), indicating that the changes occur only after a first pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)