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The peripartum period is the highest risk interval for the onset or exacerbation of psychiatric illness in women’s lives. Notably, pregnancy and childbirth have been associated with short-term structural and functional changes in the maternal human brain. Yet the long-term effects of pregnancy on maternal brain structure remain unknown. We investigated a large population-based cohort to examine the association between parity and brain structure. In total, 2,835 women (mean age 65.2 years; all free from dementia, stroke, and cortical brain infarcts) from the Rotterdam Study underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Associations of parity with global and lobar brain tissue volumes, white matter microstructure, and markers of vascular brain disease were examined using regression models. We found that parity was associated with a larger global gray matter volume (β = 0.14, 95% CI = 0.09–0.19), a finding that persisted following adjustment for sociodemographic factors. A non-significant dose-dependent relationship was observed between a higher number of childbirths and larger gray matter volume. The gray matter volume association with parity was globally proportional across lobes. No associations were found regarding white matter volume or integrity, nor with markers of cerebral small vessel disease. The current findings suggest that pregnancy and childbirth are associated with robust long-term changes in brain structure involving a larger global gray matter volume that persists for decades. Future studies are warranted to further investigate the mechanism and physiological relevance of these differences in brain morphology.

Importance: Emerging data suggest that more than two-thirds of premenstrual disorders (PMDs), including premenstrual syndrome and premenstrual dysphoric disorder, have symptom onset during the teen years. Adulthood adiposity has been associated with PMDs; however, the association with childhood and adolescent body size is unknown. Objective: To examine the association between childhood and adolescent body size and risk of PMDs in young adulthood. Design, Setting, and Participants: This prospective cohort study included 6524 US female participants from the Growing Up Today Study (1996-2013). Data were analyzed from February 26, 2020, to June 23, 2021. Exposures: Body mass index (BMI) was estimated using self-reported height and weight through adolescence and converted to BMI for age (z score). Main Outcomes and Measures: In 2013, premenstrual symptoms and identified PMDs were assessed with a validated scale based on the Calendar of Premenstrual Experiences. The associations of BMI for age with PMDs and premenstrual symptoms were examined using log-binomial and linear regressions, respectively. Results: Among 6524 participants (mean [SD] age, 26 [3.5] years; 6108 [93.6%] White), 1004 (15.4%) met the criteria for a PMD. Baseline BMI for age reported at a mean (SD) age of 12.7 (1.1) years was associated with increased risk of PMDs (confounding-adjusted relative risk, 1.09 per unit of z score; 95% CI, 1.03-1.15) and higher burden of premenstrual symptoms (β = 0.06; 95% CI, 0.04-0.08). Associations were particularly pronounced for premenstrual dysphoric disorder and for PMDs with symptom onset before 20 years of age and remained in the absence of psychiatric comorbidities, including depression, anxiety, and disordered eating behavior. When analyzing BMI change over time, individuals with high BMI throughout adolescence had a higher burden of premenstrual symptoms (β = 0.17; 95% CI, 0.08-0.27) compared with those with normal BMI throughout adolescence. Individuals with high BMI early followed by a mild decrease later did not report higher premenstrual symptoms (β = 0.06; 95% CI, 0.00-0.12). Conclusions and Relevance: In this cohort study, childhood body size was associated with PMD risk and premenstrual symptoms in young adulthood. These findings suggest that maintaining a normal body mass in childhood may be considered for lowering the burden of PMDs in adulthood..

The peripartum period is the highest risk interval for the onset or exacerbation of psychiatric illness in women's lives. Notably, pregnancy and childbirth have been associated with short-term structural and functional changes in the maternal human brain. Yet the long-term effects of pregnancy on maternal brain structure remain unknown. We investigated a large population-based cohort to examine the association between parity and brain structure. In total, 2,835 women (mean age 65.2 years; all free from dementia, stroke, and cortical brain infarcts) from the Rotterdam Study underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Associations of parity with global and lobar brain tissue volumes, white matter microstructure, and markers of vascular brain disease were examined using regression models. We found that parity was associated with a larger global gray matter volume (β = 0.14, 95% CI = 0.09-0.19), a finding that persisted following adjustment for sociodemographic factors. A non-significant dose-dependent relationship was observed between a higher number of childbirths and larger gray matter volume. The gray matter volume association with parity was globally proportional across lobes. No associations were found regarding white matter volume or integrity, nor with markers of cerebral small vessel disease. The current findings suggest that pregnancy and childbirth are associated with robust long-term changes in brain structure involving a larger global gray matter volume that persists for decades. Future studies are warranted to further investigate the mechanism and physiological relevance of these differences in brain morphology.

STUDY QUESTION Is pubertal timing associated with risk of premenstrual disorders (PMDs) in young adulthood? SUMMARY ANSWER Late pubertal development is associated with decreased premenstrual symptom burden and risk of PMDs in young adulthood. WHAT IS KNOWN ALREADY PMDs, including premenstrual syndrome and premenstrual dysphoric disorder, may begin during the teenage years. Few risk factors in early life have been identified for PMD development. STUDY DESIGN, SIZE, DURATION A prospective cohort study of 6495 female participants during 1996–2013. PARTICIPANTS/MATERIALS, SETTING, METHODS We included participants from the Growing Up Today Study (GUTS). Pubertal development was indicated by the timing of menarche, breast and pubic hair growth. Self-reported age at menarche was longitudinally assessed at enrollment (in 1996/2004 for GUTS I/II) and onwards, and classified as early (age ≤ mean − SD, 11.64 years), normative and late menarche (age ≥ mean + SD, 13.95 years). Timing of pubic hair and breast growth were assessed multiple times during follow-up via Tanner scales, and classified into early, normative and late development according to mean ± SD. Using a validated questionnaire based on the Calendar of Premenstrual Experiences, we assessed premenstrual symptoms and identified probable cases of PMDs in 2013. We examined the associations of timing of pubertal development with premenstrual symptom score and disorders using multivariable linear and logistic regressions, respectively. MAIN RESULTS AND THE ROLE OF CHANCE In 2013 (mean age = 26), 1001 (15.4%) individuals met criteria for a PMD. An inverse association was found between age at menarche and premenstrual symptom z-score (β −0.05 per year, 95% CI −0.07 to −0.03) and risk of PMDs (odds ratio (OR) 0.93 per year, 95% CI 0.88 to 0.99). Compared to individuals with normative menarche, individuals with late menarche had a lower risk of PMDs (OR 0.73, 95% CI 0.59 to 0.91), while individuals with early menarche had comparable odds (OR 0.98, 95% CI 0.81 to 1.18). Moreover, early growth of pubic hair was associated with increased premenstrual symptoms (z-score β 0.09 per year, 95% CI 0.02 to 0.17) and PMD risk (OR 1.28, 95% CI 1.04 to 1.56), independent of age at menarche. No associations were noted for breast development. LIMITATIONS, REASONS FOR CAUTION One major limitation is some misclassification of menarche due to recall. We, however, showed robust association among participants who were premenarcheal at baseline. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that pubertal timing, particularly timing of menarche, is inversely associated with the risk of developing premenstrual symptoms in young adulthood, and that women with later menarche have significantly lower risk of PMDs. Information on PMDs should be provided to teenage girls and their parents. If these findings are confirmed in independent populations, prevention strategies and early detection programs may be considered for women with early pubertal development. STUDY FUNDING/COMPETING INTEREST(S) The work is supported by the National Institutes of Health and Swedish Research Council. TRIAL REGISTRATION NUMBER N/A

Attachment instruments vary substantially in practicability of administration, employment of categorical versus dimensional scoring, quality of scales, and applicability to different attachment figures. The Attachment Network Q-sort (ANQ) is a self-report, quasi-qualitative instrument that discriminates relationship-specific attachment styles for multiple attachment figures. The current study assesses the properties of the ANQ in psychotherapy patients and in non-patient respondents, using mother, father and romantic partner as possible attachment figures. Analyzing the ANQ-data with latent class analysis, we found four types or classes of participants: a group with an overall secure profile, a group only insecure for father, a group only insecure for mother, and a group insecure for mother as well as father but not for partner (if available). These profiles proved to have good concurrent, discriminant and construct validity. We conclude that the ANQ is potentially a useful alternative clinical self-report instrument to assess combinations of attachment styles for a range of attachment figures such as parents and a romantic partner.

The levonorgestrel-releasing intrauterine device (LNG-IUD) is currently recommended as a first-line contraceptive with an exclusively local intrauterine influence. However, recent clinical trials have identified side effects of LNG-IUD that appear to be systemically mediated, including depressed mood and emotional lability.We performed two experimental studies and a cross-sectional study. For each study, women were included from three groups: LNG-IUD (0.02mg/24h), oral ethinylestradiol/levonorgestrel (0.03mg/0.15mg; EE30/LNG) and natural cycling (NC). Study 1-Salivary cortisol was measured at baseline and at defined intervals following the Trier Social Stress Test (TSST). Heart rate was monitored continuously throughout the TSST. Study 2-Salivary cortisol and serum total cortisol were evaluated relative to low-dose (1μg) adrenocorticotropic hormone (ACTH) administration. Study 3-Hair cortisol was measured as a naturalistic index of long-term cortisol exposure.Women using LNG-IUD had an exaggerated salivary cortisol response to the TSST (24.95±13.45 nmol/L, 95% CI 17.49-32.40), compared to EE30/LNG (3.27±2.83 nmol/L, 95% CI 1.71-4.84) and NC (10.85±11.03nmol/L, 95% CI 6.30-15.40) (P0.0001). Heart rate was significantly potentiated during the TSST in women using LNG-IUD (P=0.047). In response to ACTH challenge, women using LNG-IUD and EE30/LNG had a blunted salivary cortisol response, compared to NC (P0.0001). Women using LNG-IUD had significantly elevated levels of hair cortisol compared to EE30/LNG or NC (P0.0001).Our findings suggest that LNG-IUD contraception induces a centrally-mediated sensitization of both autonomic and hypothalamic-pituitary-adrenal (HPA) axis responsivity. LNG-IUD sensitization of HPA axis responsivity was observed acutely under standardized laboratory conditions, as well as chronically under naturalistic conditions.

textabstractSTUDY QUESTION Does adrenocorticotropic hormone (ACTH) induce gonadotropin release in premenopausal women? SUMMARY ANSWER Administration of ACTH stimulates gonadotropin release, most likely by stimulation of the production of cortisol, in premenopausal women. WHAT IS KNOWN ALREADY In animal models, acute activation of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to induce gonadotropin release in the presence of sufficiently high estrogen levels. However, it is unknown whether the HPA axis has a similar influence on gonadotropin release in humans. STUDY DESIGN, SIZE, DURATION This study had a mixed factorial design. A total of 60 healthy female participants participated in the experimental study. PARTICIPANTS/MATERIALS, SETTING, METHODS The study sample comprised three distinct hormonal-based populations according to their levels of progesterone (PROG) and estradiol (E2): (i) low-PROG-low-E2, (ii) low-PROG-high-E2 and (iii) high-PROG-high-E2 women. A low dose (1 μg) of ACTH was administered to all study participants. Serum steroid and gonadotropin concentrations were measured prior to, and at 30 and 90 minutes after, intravenous ACTH administration. MAIN RESULTS AND THE ROLE OF CHANCE Mean serum cortisol levels increased significantly following ACTH administration in all groups (P < 0.001). Similarly, the serum levels of 17-OH-PROG, androstenedione, dehydroepiandrosterone and testosterone increased significantly in all groups (P < 0.01). The low-PROG-high-E2 and high-PROG-high-E2 groups exhibited a significant increase in LH and FSH levels (P < 0.001), whereas the low-PROG-low-E2 group demonstrated blunted LH and FSH responses to ACTH administration (P < 0.05). LIMITATIONS, REASONS FOR CAUTION Testing was performed during the luteal phase of the natural menstrual cycle. Testing during the follicular phase might have elicited premature, or more pronounced, LH surges in response to ACTH administration. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest a novel mechanism by which the adrenal cortex functions as a mediator of gonadotropin release. These findings contribute to a greater understanding of the influence of acute stress on reproductive endocrinology. STUDY FUNDING/COMPETING INTEREST(S) Funding was received from the Erasmus University Medical Center. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER EudraCT Number 2012-005640-14.

BackgroundThe serotonin transporter gene-linked polymorphic region (5-HTTLPR) has previously been associated with hypothalamus–pituitary–adrenal axis function. Moreover, it has been suggested that this association is moderated by an interaction with stressful life experiences.AimsTo investigate the moderation of cortisol response to psychosocial stress by 5-HTTLPR genotype, either directly or through an interaction with early life stress.MethodA total of 151 women, 85 of which had personality psychopathology, performed the Trier Social Stress Test while cortisol responsivity was assessed.ResultsThe results demonstrate a main effect of genotype on cortisol responsivity. Women carrying two copies of the long version of 5-HTTLPR exhibited stronger cortisol responses to psychosocial stress than women with at least one copy of the short allele (P = 0.03). However, the proportion of the variance of stress-induced cortisol responsivity explained by 5-HTTLPR genotype was not further strengthened by including early life adversity as a moderating factor (P = 0.52).ConclusionsOur results highlight the need to clarify gender-specific biological factors influencing the serotonergic system. Furthermore, our results suggest that childhood maltreatment, specifically during the first 15 years of life, is unlikely to exert a moderating influence of large effect on the relationship between the 5-HTTLPR genotype and cortisol responsivity to psychosocial stress.Declaration of interestNone.

Background: Maladaptive emotional control is a defining feature of personality disorders. Yet little is known about the underlying physiological dynamics of emotional reactivity to psychosocial stress across distinct personality disorders. The current study compared subjective emotional responses with autonomic nervous system and HPA axis physiological responses to psychosocial stress in women with cluster C personality disorder (CPD) and borderline personality disorder (BPD). Methods: Subjective mood ratings, salivary cortisol, heart rate (HR), and skin conductance level (SCL) were assessed before, during, and after exposure to a standardized psychosocial stress paradigm (Trier Social Stress Test, TSST) in 26 women with BPD, 20 women with CPD, and 35 healthy female controls. Subjects were free of any medication including hormonal contraceptives, had a regular menstrual cycle, and were tested during the luteal phase of their menstrual cycle. Results: Both CPD and BPD patients reported a similar burden of subjective mood disturbance. However, only BPD patients demonstrated reduced baseline cortisol levels with a blunted cortisol and HR reactivity to the TSST. In addition, BPD patients exhibited a generalized increase of SCL. No significant differences in baseline or TSST reactivity of cortisol, HR, or SCL were observed between CPD patients and healthy controls. Conclusion: These findings indicate that patients with BPD have significant alterations in their physiological stress reactivity, which is notably distinct from patients with CPD and those of healthy controls. (C) 2016 Elsevier Ltd. All rights reserved.